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Amino Acids - published by Springer
Amino Acids publishes contributions from all fields of amino acid and protein research: analysis, separation, synthesis, biosynthesis, cross linking amino acids, racemization/enantiomers, modification of amino acids as phosphorylation, methylation, acetylation, glycosylation and nonenzymatic glycosylation, new roles for amino acids in physiology and pathophysiology, biology, amino acid analogues and derivatives, polyamines, radiated amino acids, peptides, stable isotopes and isotopes of amino acids. Applications in medicine, food chemistry, nutrition, gastroenterology, nephrology, neurochemistry, pharmacology, excitatory amino acids are just some of the topics covered.
The non-proteinogenic amino acids capreomycidine and epicapreomycidine are constituents of antibiotically active natural products,
but the synthesis of these unusual cyclic guanidine derivatives is challenging. The biosynthesis of capreomycidine has therefore
been employed as a guideline to develop a concise biomimetic synthesis of both epimeric amino acids. The resulting domino-guanidinylation-aza-Michael-addition
reaction provides the most convenient access to these amino acids in racemic form. Attempts to dissect the domino reaction
into two separate transformations for a stereocontrolled version of this synthetic approach have also been made. The synthesized
didehydro-arginine derivatives with urethane-protected guanidine moieties did not undergo the aza-Michael-addition anymore.
These results may have wider implications for the 1,4-addition of guanidines to ?,?-unsaturated carbonyl compounds, particularly
to didehydro amino acids.
Content Type Journal Article
Category Original Article
Pages 1-16
DOI 10.1007/s00726-012-1309-8
Authors
Martin Büschleb, Department of Chemistry, Institute of Organic and Biomolecular Chemistry, Georg-August-University Göttingen, Tammannstr. 2, 37077 Göttingen, Germany
Markus Granitzka, Department of Chemistry, Institute of Inorganic Chemistry, Georg-August-University Göttingen, Tammannstr. 4, 37077 Göttingen, Germany
Dietmar Stalke, Department of Chemistry, Institute of Inorganic Chemistry, Georg-August-University Göttingen, Tammannstr. 4, 37077 Göttingen, Germany
Christian Ducho, Department of Chemistry, Institute of Organic and Biomolecular Chemistry, Georg-August-University Göttingen, Tammannstr. 2, 37077 Göttingen, Germany
It has been demonstrated that taurine has various physiological functions in the body. We demonstrated that taurine is abundant
in the serum, liver, muscle and testis of the Japanese eel (Anguilla japonica). In the eel testis, taurine is found mainly in spermatogonia and is weakly expressed also in the Sertoli cells. We have
further found in the eel testis that taurine is actively accumulated via the sodium/chloride-dependent taurine transporter
(TauT; SLC6A6), which is expressed in germ cells. In our current study, the effects of taurine on the anti-oxidant response
were examined. Taurine was found to promote the total superoxide dismutase (SOD) activity in the testis. Moreover, our results
indicate that taurine does not affect the mRNA levels of copper–zinc (Cu/Zn) SOD or manganese SOD, but promotes the translation
of Cu/Zn SOD. Overall, our present data suggest that taurine may modulate Cu/Zn SOD at the translational level and thereby
may play an important role in the protection of germ cells from oxidative stress.
Content Type Journal Article
Category Original Article
Pages 1-11
DOI 10.1007/s00726-012-1316-9
Authors
Masato Higuchi, Research Group for Reproductive Physiology, South Ehime Fisheries Research Center, Ehime University, Ainan, Ehime, Japan
Fritzie T. Celino, School of Aquatic and Fishery Sciences, University of Washington, Seattle, WA 98195, USA
Sonoko Shimizu-Yamaguchi, Ainan Fishery Cooperation Union, Ainan, Ehime, Japan
Chiemi Miura, Research Group for Reproductive Physiology, South Ehime Fisheries Research Center, Ehime University, Ainan, Ehime, Japan
Takeshi Miura, Research Group for Reproductive Physiology, South Ehime Fisheries Research Center, Ehime University, Ainan, Ehime, Japan
Modafinil has been shown to modify behavioural and cognitive functions and to effect several brain receptors. Effects, however,
were not observed at the receptor protein complex level and it was therefore the aim of the study to train mice in the multiple
T-Maze (MTM) as a paradigm for spatial memory and to determine paralleling brain receptor complex levels. Sixty C57BL/6J mice
were used in the study and divided into four groups (trained drug injected; trained vehicle injected; yoked drug injected;
yoked vehicle injected). Animals obtained training for 4 days and were killed 6 h following the last training session on day
4. Hippocampi were dissected from the brain, membrane fractions were prepared by ultracentrifugation and were run on blue-native
gels and immunoblotted with antibodies against major brain receptors. Modafinil treatment led to decreased latency and increased
average speed, but not to changes in pathlength and number of correct decisions in the MTM. Drug effects were modifying receptor
complexes of GluR1, GluR2, D2 and NR1. Training effects on receptor complex levels were observed for GluR3, D1 and nicotinic
acetylcholine receptor alpha 7 (Nic7). GluR1 levels were correlating with GluR2 and D1 levels were correlating with D2 and
NR1. Involvement of the glutamatergic, NMDA, dopaminergic and nicotinergic system in modafinil and memory training were herein
described for the first time. A brain receptor complex pattern was revealed showing the concerted action following modafinil
treatment.
Content Type Journal Article
Category Original Article
Pages 1-8
DOI 10.1007/s00726-012-1306-y
Authors
Sunetra Sase, Department of Pediatrics, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria
Deeba Khan, Department of Pediatrics, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria
Fernando Sialana, Department of Pediatrics, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria
Harald Höger, Core Unit of Biomedical Research, Division of Laboratory Animal Science and Genetics, Medical University of Vienna, Brauhausgasse 34, 2325 Himberg, Austria
Nina Russo-Schlaff, Department of Pediatrics, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria
Gert Lubec, Department of Pediatrics, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria
Condensation reactions of amino acid (glycine and alanine) on the surface of metal(II) octacyanomolybdate(IV) (MOCMo) complexes
are investigated using high-performance liquid chromatography (HPLC) and electron spray ionizations–mass spectroscopy (ESI–MS).
The series of MOCMo have been synthesized and the effect of outer sphere metal ions present in the MOCMo on the oligomerization
of glycine and alanine at different temperature and time found out. Formation of peptides was observed to start after 7 days
at 60 °C. Maximum yield of peptides was found after 35 days at 90 °C. It has been found that zinc(II) octacyanomolybdate(IV)
and cobalt(II) were the most effective metal cations present in outer sphere of the MOCMo for the production of high yield
of oligomerized products. Surface area of MOCMo seems to play dominating parameter for the oligomerization of alanine and
glycine. The results of the present study reveal the role of MOCMo in chemical evolution for the oligomerization of biomolecules.
Content Type Journal Article
Category Original Article
Pages 1-13
DOI 10.1007/s00726-012-1320-0
Authors
Anand Kumar, Department of Chemistry, Indian Institute of Technology Roorkee, Roorkee, 247667 India
Kamaluddin, Department of Chemistry, Indian Institute of Technology Roorkee, Roorkee, 247667 India
CMS1MS2 (CC-Ib) from Carica candamarcensis (Vasconcellea cundinamarcensis) is a cysteine proteinase found as a single polypeptide containing 213 residues of 22,991 Da. The enzyme was purified by
three chromatographic steps, two of them involving cationic exchange. Crystals of CMS1MS2 complexed with E-64 were obtained
by the hanging drop vapor-diffusion method at 291 K using ammonium sulfate and polyethylene glycol 4000/8000 as precipitant.
The complex CMS1MS2-E-64 crystallized in the tetragonal space group P41212 with unit-cell parameters; a = b = 73.64, c = 118.79 Å. The structure was determined by Molecular Replacement and refined at 1.87 Å resolution to a final R factor of 16.2 % (Rfree = 19.3 %). Based on the model, the structure of CMS1MS2 (PDB 3IOQ) ranks as one of the least basic cysteine isoforms from
C. candamarcensis, is structurally closer to papain, caricain, chymopapain and mexicain than to the other cysteine proteinases, while its activity
is twice the activity of papain towards BAPNA substrate. Two differences, one in the S2 subsite and another in the S3 subsite
of CMS1MS2 may contribute to the enhanced activity relative to papain. In addition, the model provides a structural basis
for the sensitivity of CMS1MS2 to inhibition by cystatin, not shown by other enzymes of the group, e.g., glycyl endopeptidase
and CMS2MS2.
Content Type Journal Article
Category Original Article
Pages 1-11
DOI 10.1007/s00726-012-1318-7
Authors
Marco T. R. Gomes, Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av. Antônio Carlos 6627, Belo Horizonte, MG 31270-901, Brazil
Raphael D. Teixeira, Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av. Antônio Carlos 6627, Belo Horizonte, MG 31270-901, Brazil
Míriam T. P. Lopes, Departamento de Farmacologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av. Antônio Carlos 6627, Belo Horizonte, MG 31270-901, Brazil
Ronaldo A. P. Nagem, Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av. Antônio Carlos 6627, Belo Horizonte, MG 31270-901, Brazil
Carlos E. Salas, Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av. Antônio Carlos 6627, Belo Horizonte, MG 31270-901, Brazil
Amino acids are known to elicit complex taste, but most human psychophysical studies on the taste of amino acids have focused
on a single basic taste, such as umami (savory) taste, sweetness, or bitterness. In this study, we addressed the potential
relationship between the structure and the taste properties of amino acids by measuring the human gustatory intensity and
quality in response to aqueous solutions of proteogenic amino acids in comparison to d-enantiomers. Trained subjects tasted aqueous solution of each amino acid and evaluated the intensities of total taste and
each basic taste using a category-ratio scale. Each basic taste of amino acids showed the dependency on its hydrophobicity,
size, charge, functional groups on the side chain, and chirality of the alpha carbon. In addition, the overall taste of amino
acid was found to be the combination of basic tastes according to the partial structure. For example, hydrophilic non-charged
middle-sized amino acids elicited sweetness, and l-enantiomeric hydrophilic middle-sized structure was necessary for umami taste. For example, l-serine had mainly sweet and minor umami taste, and d-serine was sweet. We further applied Stevens’ psychophysical function to relate the total-taste intensity and the concentration,
and found that the slope values depended on the major quality of taste (e.g., bitter large, sour small).
Content Type Journal Article
Category Original Article
Pages 1-10
DOI 10.1007/s00726-012-1315-x
Authors
Misako Kawai, Section of Oral Neuroscience, Graduate School of Dental Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582 Japan
Yuki Sekine-Hayakawa, Institute for Innovation, Ajinomoto Co., Inc., 1-1 Suzuki-cho, Kawasaki-Ku, Kawasaki, 210-8582 Japan
Atsushi Okiyama, Quality Assurance & External Scientific Affairs, Ajinomoto Co., Inc., 1-15-1 Kyobashi, Chuo-Ku, Tokyo, 104-8315 Japan
Yuzo Ninomiya, Section of Oral Neuroscience, Graduate School of Dental Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582 Japan
A comparative proteomic study was performed to unravel the protein networks involved in cadmium stress response in soybean.
Ten-day-old seedlings of contrasting cadmium accumulating soybean cultivars—Harosoy (high cadmium accumulator), Fukuyutaka
(low cadmium accumulator), and their recombinant inbred line CDH-80 (high cadmium accumulator) were exposed to 100 ?M CdCl2 treatment for 3 days. Root growth was found to be affected under cadmium stress in all. Varietal differences at root protein
level were evaluated. NADP-dependent alkenal double bond reductase P1 was found to be more abundant in low cadmium accumulating
Fukuyutaka. Leaf proteome analysis revealed that differentially expressed proteins were primarily involved in metabolism and
energy production. The results indicate that both high and low cadmium accumulating cultivars and CDH-80 share some common
defense strategies to cope with the cadmium stress. High abundance of enzymes involved in glycolysis and TCA cycle might help
cadmium challenged cells to produce more energy necessary to meet the high energy demand. Moreover, enhanced expressions of
photosynthesis related proteins indicate quick utilization of photoassimilates in energy generation. Increased abundance of
glutamine synthetase in all might be involved in phytochelatin mediated detoxification of cadmium ions. In addition, increased
abundance of antioxidant enzymes, namely superoxide dismutase, ascorbate peroxidase, catalase, ensures cellular protection
from reactive oxygen species mediated damages under cadmium stress. Enhanced expression of molecular chaperones in high cadmium
accumulating cultivar might be another additional defense mechanism for refolding of misfolded proteins and to stabilize protein
structure and function, thus maintain cellular homeostasis.
Content Type Journal Article
Category Original Article
Pages 1-24
DOI 10.1007/s00726-012-1319-6
Authors
Zahed Hossain, National Institute of Crop Science, Kannondai 2-1-18, Tsukuba, 305-8518 Japan
Makita Hajika, National Institute of Crop Science, Kannondai 2-1-18, Tsukuba, 305-8518 Japan
Setsuko Komatsu, National Institute of Crop Science, Kannondai 2-1-18, Tsukuba, 305-8518 Japan
The oral administration of proline, one of the non-essential amino acids, has been shown to effectively protect the liver
from d-galactosamine (GalN)-induced liver injury and to improve the survival rate. The aim of this study was to investigate the
mechanism of this protective action of proline. We paid particular attention to the effect of proline on inflammatory activation,
regenerative response, and the associated signal transduction in the liver. Male Fischer rats received intraperitoneal injections
of GalN (1.4 g/kg) with or without the oral administration of proline (2 g/kg) 1 h before GalN treatment. Liver pathology,
plasma indices of inflammation, and the level of proliferative marker in the liver were monitored. The hepatic activation
of interleukin-6 (IL-6)/signal transducer and activator of transcription (STAT)-3 pathway, which is downstream of tumor necrosis
factor (TNF)-?/nuclear factor-?B, was also studied. GalN induced massive inflammatory expansion in the liver, leading to a
high death rate (60 %) more than 72 h after the treatment. Proline administration significantly suppressed inflammatory infiltration
in the live after 48 h, which was accompanied by depletion of plasma TNF-?, glutamic oxaloacetic transaminase, and glutamic
pyruvic transaminase. The mRNA expression of histone H3, a marker of proliferation, was significantly upregulated in the liver
of proline-treated animals. Furthermore, IL-6/STAT-3 pathway, an anti-inflammatory and regenerative signaling pathway, was
strongly activated prior to these observations, with the upregulated expression of downstream genes. These results suggest
that the tissue-protective mechanism of proline involves the early activation of IL-6/STAT-3 pathway in the liver, with subsequent
activation of the regenerative response and suppression of massive inflammatory activation.
Content Type Journal Article
Category Original Article
Pages 1-10
DOI 10.1007/s00726-012-1317-8
Authors
Yoko Obayashi, Research Institute for Health Fundamentals, Ajinomoto Co., Inc, 1-1 Suzuki-cho, Kawasaki-ku, Kawasaki, Kanagawa, 210-8681 Japan
Harumi Arisaka, Research Institute for Health Fundamentals, Ajinomoto Co., Inc, 1-1 Suzuki-cho, Kawasaki-ku, Kawasaki, Kanagawa, 210-8681 Japan
Shintaro Yoshida, Research Institute for Health Fundamentals, Ajinomoto Co., Inc, 1-1 Suzuki-cho, Kawasaki-ku, Kawasaki, Kanagawa, 210-8681 Japan
Masato Mori, Research Institute for Health Fundamentals, Ajinomoto Co., Inc, 1-1 Suzuki-cho, Kawasaki-ku, Kawasaki, Kanagawa, 210-8681 Japan
Michio Takahashi, Research Institute for Health Fundamentals, Ajinomoto Co., Inc, 1-1 Suzuki-cho, Kawasaki-ku, Kawasaki, Kanagawa, 210-8681 Japan
This article examines the actions of taurine on models of renal dysfunction, the potential mechanisms of taurine action and
the possible clinical significance of these findings. Our laboratory has written previously on the role of taurine in renal
function and we have focused upon the normal physiology of the kidney and on the mechanisms and regulation of the renal transport
of taurine. This review is a distinct change of emphasis in that we describe a number of studies which have evaluated various
aspects of renal dysfunction, including hypertension and proteinuria, specific glomerular and tubular disorders, acute and
chronic renal conditions, urinary tract conditions including infection and nephrolithiasis, and diabetic nephropathy. The
subject of chronic kidney disease and renal transplantation will also be examined relative to ? amino acid. The studies evaluated
will be mainly recent ones, recognizing that older reviews of the role of this taurine in the kidney are available.
Content Type Journal Article
Category Invited Review
Pages 1-15
DOI 10.1007/s00726-012-1314-y
Authors
Xiaobin Han, Department of Pediatrics, The University of Tennessee Health Science Center, and the Children’s Foundation Research Institute at Le Bonheur Children’s Hospital, Memphis, TN 38103, USA
Russell W. Chesney, Department of Pediatrics, The University of Tennessee Health Science Center, and the Children’s Foundation Research Institute at Le Bonheur Children’s Hospital, Memphis, TN 38103, USA
Pyrococcus horikoshii lysyl-tRNA synthetase/tRNA orthogonal pair exhibited high selectivity towards d-lysine in the presence of excess amount of d-lysine. Based on the observation, this orthogonal pair was employed to encode d-lysine, and d-lysine was site-specifically incorporated into the diketoreductase in E. coli cells.
Graphical abstract
Content Type Journal Article
Category Short Communication
Pages 1-7
DOI 10.1007/s00726-012-1311-1
Authors
Zhizhi Liu, Laboratory of Chemical Biology, State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tongjia Street, Nanjing, 210009 Jiangsu, People’s Republic of China
Xin Yang, Laboratory of Chemical Biology, State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tongjia Street, Nanjing, 210009 Jiangsu, People’s Republic of China
Denghuan Yi, Laboratory of Chemical Biology, State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tongjia Street, Nanjing, 210009 Jiangsu, People’s Republic of China
Shuzhen Wang, Laboratory of Chemical Biology, State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tongjia Street, Nanjing, 210009 Jiangsu, People’s Republic of China
Yijun Chen, Laboratory of Chemical Biology, State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tongjia Street, Nanjing, 210009 Jiangsu, People’s Republic of China
Glutamate dehydrogenase (GDH) plays a crucial role in amino acid deamination and has been used as an inductor of nutrients
metabolism. In this study, we cloned and analyzed the GDH cDNAs in diploids (red crucian carp), triploids and tetraploids
and characterized their expression profiles upon dietary treatments. Results showed a high sequence similarity of GDH among
the three kinds of ploidy fishes and other vertebrates. Expression analysis revealed that GDH exhibited a distinct spatial
pattern of expression in different types of fishes. The triploids and tetraploids had higher levels of expression than diploids
in heart, liver, gill, muscle, fore-gut and mid-gut. The GDH expression was also developmentally regulated with a stronger
expression around blastula stage. The maternal GDH transcripts were first detected from eggs and their expression dropped
down from the gastrula stage to heart beat stage. Adult triploids showed the highest levels of GDH expression in liver during
breeding season which may contribute to the good appetite and fast growth. In addition, triploids exhibited high growth rates
and excess GDH expression compared with other two types of fishes. The liver GDH enzyme activities were also higher in triploids
than red crucian carp and tetraploids. Moreover, GDH expression is regulated by dietary protein levels. Fish fed with either
high or low protein diets showed higher levels of GDH expression. In summary, our results demonstrated for the first time
that the different ploidy fishes had different patterns of GDH mRNA expression during development, breeding and non-breeding
seasons, and as well dietary effects from different protein levels in diet. These data indicate that abundant GDH expression
may play an important role in growth rates in triploids.
Content Type Journal Article
Category Original Article
Pages 1-10
DOI 10.1007/s00726-012-1313-z
Authors
Zhen Liu, Key Laboratory of Protein Chemistry and Developmental Biology of State Education Ministry of China, College of Life Sciences, Hunan Normal University, Changsha, 410081 China
Yi Zhou, Key Laboratory of Protein Chemistry and Developmental Biology of State Education Ministry of China, College of Life Sciences, Hunan Normal University, Changsha, 410081 China
Shaojun Liu, Key Laboratory of Protein Chemistry and Developmental Biology of State Education Ministry of China, College of Life Sciences, Hunan Normal University, Changsha, 410081 China
Huan Zhong, Key Laboratory of Protein Chemistry and Developmental Biology of State Education Ministry of China, College of Life Sciences, Hunan Normal University, Changsha, 410081 China
Chun Zhang, Key Laboratory of Protein Chemistry and Developmental Biology of State Education Ministry of China, College of Life Sciences, Hunan Normal University, Changsha, 410081 China
Xuewei kang, Key Laboratory of Protein Chemistry and Developmental Biology of State Education Ministry of China, College of Life Sciences, Hunan Normal University, Changsha, 410081 China
Yun Liu, Key Laboratory of Protein Chemistry and Developmental Biology of State Education Ministry of China, College of Life Sciences, Hunan Normal University, Changsha, 410081 China
A novel fluorescent amino acid, l-4-chloromethylcoumarin-6-yl-alanine, was obtained from tyrosine by a Pechmann reaction. The assembly of the heterocyclic
ring at the tyrosine side chain could be achieved before or after incorporation of tyrosine into a dipeptide, and amino acid
and dipeptide ester conjugates were obtained by coupling to a model N-protected alanine. The behaviour of one of the fluorescent conjugates towards irradiation was studied in a photochemical
reactor at different wavelengths (254, 300, 350 and 419 nm). The photoreaction course in methanol/HEPES buffer solution (80:20)
was followed by HPLC/UV monitoring. It was found that the novel unnatural amino acid could act as a fluorescent label, due
to its fluorescence properties, and, more importantly, as a photoactivable unit, due to the short irradiation times necessary
to cleave the ester bond between the model amino acid and the coumarin-6-yl-alanine.
Content Type Journal Article
Category Original Article
Pages 1-10
DOI 10.1007/s00726-012-1310-2
Authors
Andrea S. C. Fonseca, Centro de Química, Universidade do Minho, Campus de Gualtar, 4710-057 Braga, Portugal
M. Sameiro T. Gonçalves, Centro de Química, Universidade do Minho, Campus de Gualtar, 4710-057 Braga, Portugal
Susana P. G. Costa, Centro de Química, Universidade do Minho, Campus de Gualtar, 4710-057 Braga, Portugal
Glutamine and leucine are important mTORC1 modulators, although their roles are not precisely defined. In HepG2 and HeLa cells
glutamine-free incubation lowers mTORC1 activity, although cell leucine is not decreased. mTORC1 activity, suppressed by amino
acid-free incubation, is completely rescued only if essential amino acids (EAA) and glutamine are simultaneously restored,
although cell leucine is higher in the absence than in the presence of glutamine. Thus, glutamine stimulates mTORC1 independent
of cell leucine, suggesting the existence of two distinct stimulatory signals from either glutamine or EAA.
Content Type Journal Article
Category Short Communication
Pages 1-7
DOI 10.1007/s00726-012-1312-0
Authors
Martina Chiu, Unit of General and Clinical Pathology, Department of Experimental Medicine, University of Parma, Via Volturno 39, 43125 Parma, Italy
Saverio Tardito, Unit of General and Clinical Pathology, Department of Experimental Medicine, University of Parma, Via Volturno 39, 43125 Parma, Italy
Amelia Barilli, Unit of General and Clinical Pathology, Department of Experimental Medicine, University of Parma, Via Volturno 39, 43125 Parma, Italy
Massimiliano G. Bianchi, Unit of General and Clinical Pathology, Department of Experimental Medicine, University of Parma, Via Volturno 39, 43125 Parma, Italy
Valeria Dall’Asta, Unit of General and Clinical Pathology, Department of Experimental Medicine, University of Parma, Via Volturno 39, 43125 Parma, Italy
Ovidio Bussolati, Unit of General and Clinical Pathology, Department of Experimental Medicine, University of Parma, Via Volturno 39, 43125 Parma, Italy
The role of polyamines in renal physiology is only partially understood. Moreover, most of the data on the enzymes of polyamine
metabolism come from studies using whole kidneys. The aim of the present study was to analyze the mRNA abundance of the genes
implicated in both the polyamine biosynthetic and catabolic pathways in different renal zones of male and female mice, by
means of the quantitative reverse transcription-polymerase chain reaction. Our results indicate that there is an uneven distribution
of the different mRNAs studied in the five renal zones: superficial cortex, deep cortex, outer stripe of the outer medulla
(OS), inner stripe of the outer medulla (IS), and the inner medulla + papilla (IM). The biosynthetic genes, ornithine decarboxylase
(ODC) and spermine synthase, were more expressed in the cortex, whereas the mRNAs of the catabolic genes spermine oxidase
(SMO) and diamine oxidase were more abundant in IS and IM. The genes involved in the regulation of polyamine synthesis (AZ1,
AZ2 and AZIN1) were expressed in all the renal zones, predominantly in the cortex, while AZIN2 gene was more abundant in the
OS. ODC, SMO, spermidine synthase and spermidine/spermine acetyl transferase expression was higher in males than in females.
In conclusion, the genes encoding for the polyamine metabolism were specifically and quantitatively distributed along the
corticopapillary axis of male and female mouse kidneys, suggesting that their physiological role is essential in defined renal
zones and/or nephron segments.
Content Type Journal Article
Category Original Article
Pages 1-11
DOI 10.1007/s00726-012-1300-4
Authors
Olivier Levillain, Institut de Biologie et Chimie des Protéines, FRE 3310 “Dysfonctionnements de l’homéostasie tissulaire et ingénierie thérapeutique” (DyHTIT), 7 passage du Vercors, 69367 Lyon, France
Bruno Ramos-Molina, Department of Biochemistry and Molecular Biology B and Immunology, Faculty of Medicine, University of Murcia, Campus de Espinardo, 30100 Murcia, Spain
Fabien Forcheron, Department EBR, IRBA-CRSSA La Tronche, La Tronche, France
Rafael Peñafiel, Department of Biochemistry and Molecular Biology B and Immunology, Faculty of Medicine, University of Murcia, Campus de Espinardo, 30100 Murcia, Spain
This study determined changes in plasma amino acid concentration in late-gestating (beginning 58 ± 1.02 days prior to calving),
primiparous, winter-grazing range heifers receiving wheat middling-based supplement without (CON) or with rumen-protected
methionine (MET) to provide 15 g dl-MET each day. Plasma was collected on days ?2 and 0 (start of MET supplementation just prior to individually receiving supplement
at 0700 hours). Plasma was sampled again on days 40, 42 and 44 prior to supplementation at 0700 and 1100 hours (4 h after
receiving daily supplement). Data were analyzed with cow as the experimental unit. Continuous variables were analyzed by the
main effects of treatment, date, or time and their interaction when appropriate. Comparable BW (P = 0.32) and BCS (P = 0.83) over the 44-day metabolism trial were found between both CON- and MET-fed heifers. MET-supplemented heifers had greater
(P < 0.01) plasma concentrations of methionine indicating that the rumen-protection technology successfully delivered methionine
to the small intestine. Supplementation with rumen-protected dl-MET caused a significant supplement × date interaction for glutamine (P = 0.03), glycine (P = 0.02), methionine (P < 0.01), and serine (P = 0.05). In addition, trends for supplement × date interactions were detected for leucine (P = 0.07), threonine (P = 0.09), valine (P = 0.08), total amino acids (TAA; P = 0.08), non essential amino acids (NEAA; P = 0.08), branched chain amino acids (BCAA; P = 0.08), and glucogenic amino acids (GLUCO; P = 0.08). These results suggest that the BCAA (leucine and valine) were utilized more efficiently with MET supplemented heifers
compared to CON supplemented heifers. Plasma AA concentrations for glutamic acid (P < 0.01), histidine (P = 0.01), tyrosine (P < 0.01), and EAA (P < 0.01), all decreased throughout the study. These results further confirm methionine is a limiting amino acid in forage
fed late-gestating heifers and further suggests the limitation when grazing dormant range forages as shown by improved utilization
of other plasma amino acids when supplemental methionine was provided.
Content Type Journal Article
Category Original Article
Pages 1-13
DOI 10.1007/s00726-012-1301-3
Authors
Richard C. Waterman, Fort Keogh Livestock and Range Research Laboratory, United States Department of Agriculture, Agricultural Research Service, 243 Fort Keogh Road, Miles City, MT 59301, USA
Valerie L. Ujazdowski, School of Veterinary Medicine, University of Wisconsin, Madison, WI 53706, USA
Mark K. Petersen, Fort Keogh Livestock and Range Research Laboratory, United States Department of Agriculture, Agricultural Research Service, 243 Fort Keogh Road, Miles City, MT 59301, USA
Gonococcal growth inhibitor 1 (GGI-1) is a 44-residue peptide with potent anti-Legionella activity. It has been isolated from Staphylococcus haemolyticus but, to date, its chemical synthesis has not been reported. Acquisition of this peptide via this means would enable a more
detailed examination of its antimicrobial properties. However, its synthesis represents a significant challenge because of
two predicted “difficult sequences” within the peptide. Its successful solid-phase assembly is reported in this paper, and
was accomplished by use of simple palliative measures including the introduction of a single pseudo-proline isostere in order
to counteract on-resin aggregation. The peptide had moderate antimicrobial activity against Escherichia coli but was inactive against another Gram-negative bacterium and two Gram-positive bacteria (Bacillus species). It had significant haemolytic activity, with a H50 (concentration of peptide that causes 50 % haemolysis) of 20 and 125 ?M for two blood samples from different donors. An alternative
therapeutic index to that proposed for GGI-1 in a recent publication is proposed.
Content Type Journal Article
Category Original Article
Pages 1-5
DOI 10.1007/s00726-012-1305-z
Authors
John D. Wade, Florey Neuroscience Institutes, University of Melbourne, Melbourne, VIC 3010, Australia
Feng Lin, Florey Neuroscience Institutes, University of Melbourne, Melbourne, VIC 3010, Australia
Mohammed Akhter Hossain, Florey Neuroscience Institutes, University of Melbourne, Melbourne, VIC 3010, Australia
Raymond M. Dawson, Defence Science and Technology Organisation, 506 Lorimer Street, Fishermans Bend, Melbourne, VIC 3207, Australia
We present here the 2011 update of the AutoMotif Service (AMS 4.0) that predicts the wide selection of 88 different types
of the single amino acid post-translational modifications (PTM) in protein sequences. The selection of experimentally confirmed
modifications is acquired from the latest UniProt and Phospho.ELM databases for training. The sequence vicinity of each modified
residue is represented using amino acids physico-chemical features encoded using high quality indices (HQI) obtaining by automatic
clustering of known indices extracted from AAindex database. For each type of the numerical representation, the method builds
the ensemble of Multi-Layer Perceptron (MLP) pattern classifiers, each optimising different objectives during the training
(for example the recall, precision or area under the ROC curve (AUC)). The consensus is built using brainstorming technology,
which combines multi-objective instances of machine learning algorithm, and the data fusion of different training objects
representations, in order to boost the overall prediction accuracy of conserved short sequence motifs. The performance of
AMS 4.0 is compared with the accuracy of previous versions, which were constructed using single machine learning methods (artificial
neural networks, support vector machine). Our software improves the average AUC score of the earlier version by close to 7 %
as calculated on the test datasets of all 88 PTM types. Moreover, for the selected most-difficult sequence motifs types it
is able to improve the prediction performance by almost 32 %, when compared with previously used single machine learning methods.
Summarising, the brainstorming consensus meta-learning methodology on the average boosts the AUC score up to around 89 %,
averaged over all 88 PTM types. Detailed results for single machine learning methods and the consensus methodology are also
provided, together with the comparison to previously published methods and state-of-the-art software tools. The source code
and precompiled binaries of brainstorming tool are available at http://code.google.com/p/automotifserver/ under Apache 2.0 licensing.
Content Type Journal Article
Category Original Article
Pages 1-10
DOI 10.1007/s00726-012-1290-2
Authors
Dariusz Plewczynski, Interdisciplinary Centre for Mathematical and Computational Modelling, University of Warsaw, 5a Street, 02-106 Warsaw, Poland
Subhadip Basu, Department of Computer Science and Engineering, Jadavpur University, Kolkata, 700032 India
Indrajit Saha, Interdisciplinary Centre for Mathematical and Computational Modelling, University of Warsaw, 5a Street, 02-106 Warsaw, Poland
Elevated plasma concentrations of asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) were found in various
clinical settings including coronary heart disease. To assess ADMA and SDMA diagnostic validity in patients with different
stages of ischemic heart disease, we studied these markers in patients having stable angina pectoris (SAP), unstable angina
(USAP), and acute myocardial infarction (AMI). The results were compared with the values of healthy individuals. Plasma ADMA
and SDMA levels were measured by high-performance liquid chromatography. In all patient groups both markers were significantly
elevated in comparison with control ones (p < 0.001). In SAP patients, the median ADMA value was 0.75 (0.31–2.73) ?mol/L, and SDMA 1.11 (0.69–0.1.42) ?mol/L, in USAP
patients, the marker values were 0.94 (0.34–3.13) ?mol/L and 1.23 (0.88–4.72) ?mol/L, and in AMI patients, 0.98 (0.48–2.01) ?mol/L
and 1.26 (0.75–2.93) ?mol/L, while in healthy subjects they were 0.31 (0.17–0.87) ?mol/L and 0.29 (0.20–0.83) ?mol/L, respectively.
SDMA was found significantly different in SAP and AMI patients (p < 0.05). Diagnostic accuracy was determined by receiver operating characteristic (ROC) curve analysis. The highest area under
the ROC (AUC) for ADMA was obtained in AMI patients (0.976), while for SDMA in USAP patients (1.000). There was no significant
difference between the AUCs. The greatest sensitivity and specificity were found in the USAP group (95.65 and 96.30 % for
ADMA, and 100 % for each characteristic of SDMA). Considering these results, SDMA showed better clinical accuracy in assessing
ischemic disease, where it could be used as a valid marker and a therapeutic target.
Content Type Journal Article
Category Original Article
Pages 1-8
DOI 10.1007/s00726-012-1307-x
Authors
B. V. Djordjevi?, Faculty of Medicine, Institute of Biochemistry, Niš, Serbia
R. Pavlovi?, Department of Chemistry, Faculty of Medicine, University of Nis, Niš, Serbia
V. ?osi?, Centre for Medical Biochemistry, Clinical Centre Nis, Niš, Serbia
M. Deljanin-Ili?, Institute for Cardiovascular and Rheumatic Diseases, Niška Banja, Niš, Serbia
T. Risti?, Centre for Medical Biochemistry, Clinical Centre Nis, Niš, Serbia
N. Krsti?, Clinic for Cardiovascular Diseases, Clinical Centre Nis, Niš, Serbia
T. Jevtovi?-Stoimenov, Faculty of Medicine, Institute of Biochemistry, Niš, Serbia
Corynebacterium glutamicum ATCC13032 and Brevibacterium flavum JV16 were engineered for l-valine production by over-expressing ilvEBNrC genes at 31 °C in 72 h fermentation. Different strategies were carried out to reduce the by-products’ accumulation in l-valine fermentation and also to increase the availability of precursor for l-valine biosynthesis. The native promoter of ilvA of C. glutamicum was replaced with a weak promoter MPilvA (P-ilvAM1CG) to reduce the biosynthetic rate of l-isoleucine. Effect of different relative dissolved oxygen on l-valine production and by-products’ formation was recorded, indicating that 15 % saturation may be the most appropriate relative
dissolved oxygen for l-valine fermentation with almost no l-lactic acid and l-glutamate formed. To minimize l-alanine accumulation, alaT and/or avtA was inactivated in C. glutamicum and B. flavum, respectively. Compared to high concentration of l-alanine accumulated by alaT inactivated strains harboring ilvEBNrC genes, l-alanine concentration was reduced to 0.18 g/L by C. glutamicum ATCC13032MPilvA?avtA pDXW-8-ilvEBNrC, and 0.22 g/L by B. flavum JV16avtA::Cm pDXW-8-ilvEBNrC. Meanwhile, l-valine production and conversion efficiency were enhanced to 31.15 g/L and 0.173 g/g by C. glutamicum ATCC13032MPilvA?avtA pDXW-8-ilvEBNrC, 38.82 g/L and 0.252 g/g by B. flavum JV16avtA::Cm pDXW-8-ilvEBNrC. This study provides combined strategies to improve l-valine yield by minimization of by-products’ production.
Content Type Journal Article
Category Original Article
Pages 1-11
DOI 10.1007/s00726-012-1308-9
Authors
Xiaohu Hou, Laboratory of Renewable Energy and Gas Hydrate, Chinese Academy of Sciences, Guangzhou, 510640 People’s Republic of China
Xinde Chen, Laboratory of Renewable Energy and Gas Hydrate, Chinese Academy of Sciences, Guangzhou, 510640 People’s Republic of China
Yue Zhang, The Key Laboratory of Industrial Biotechnology, Ministry of Education, School of Biotechnology, JiangNan University, 1800# Lihu Road, JiangSu Province, Wuxi, 214122 People’s Republic of China
He Qian, The Key Laboratory of Industrial Biotechnology, Ministry of Education, School of Biotechnology, JiangNan University, 1800# Lihu Road, JiangSu Province, Wuxi, 214122 People’s Republic of China
Weiguo Zhang, The Key Laboratory of Industrial Biotechnology, Ministry of Education, School of Biotechnology, JiangNan University, 1800# Lihu Road, JiangSu Province, Wuxi, 214122 People’s Republic of China
Two novel cyclic hexapeptides, designated NW-G10 (1) and NW-G11 (2), were isolated from the fermentation broth of Streptomyces alboflavus 313. Their relative structures were elucidated on the basis of extensive spectroscopic analysis, and the absolute configurations
of several constituent amino acids were determined by Marfey’s method. NW-G10 (1) and NW-G11 (2) exhibited significant activity against Gram-positive bacteria, such as Bacillus cereus, Bacillus subtilis and Staphylococcus aureus, including methicillin-resistant Staphylococcus aureus (MRSA), but they are not active against gram negatives.
Content Type Journal Article
Category Original Article
Pages 1-8
DOI 10.1007/s00726-012-1303-1
Authors
Shaopeng Wei, College of Plant Protection, Northwest A&F University, Yangling, 712100 Shaanxi, People’s Republic of China
Lixia Fan, Shaanxi Province Key Laboratory of Research and Development on Botanical Pesticide, Northwest A&F University, Yangling, 712100 Shaanxi, People’s Republic of China
Wenjun Wu, Shaanxi Province Key Laboratory of Research and Development on Botanical Pesticide, Northwest A&F University, Yangling, 712100 Shaanxi, People’s Republic of China
Zhiqin Ji, College of Plant Protection, Northwest A&F University, Yangling, 712100 Shaanxi, People’s Republic of China
Two antimicrobial cryptopeptides from the N1 domain of bovine lactoferrin, lactoferricin (LFcin17–30) and lactoferrampin (LFampin265–284),
together with a hybrid version (LFchimera), were tested against the protozoan parasite Leishmania. All peptides were leishmanicidal against Leishmania donovani promastigotes, and LFchimera showed a significantly higher activity over its two composing moieties. Besides, it was the
only peptide active on Leishmania pifanoi axenic amastigotes, already showing activity below 10 ?M. To investigate their leishmanicidal mechanism, promastigote membrane
permeabilization was assessed by decrease of free ATP levels in living parasites, entrance of the vital dye SYTOX Green (MW = 600 Da)
and confocal and transmission electron microscopy. The peptides induced plasma membrane permeabilization and bioenergetic
collapse of the parasites. To further clarify the structural traits underlying the increased leishmanicidal activity of LFchimera,
the activity of several analogues was assessed. Results revealed that the high activity of these hybrid peptides seems to
be related to the order and sequence orientation of the two cryptopeptide moieties, rather than to their particular linkage
through an additional lysine, as in the initial LFchimera. The incorporation of both antimicrobial cryptopeptide motifs into
a single linear sequence facilitates chemical synthesis and should help in the potential clinical application of these optimized
analogues.
Content Type Journal Article
Category Original Article
Pages 1-13
DOI 10.1007/s00726-012-1304-0
Authors
Tânia Silva, Departamento de Química e Bioquímica, Faculdade de Ciências, Centro Investigação em Química CIQ(UP), Universidade do Porto, Rua do Campo Alegre, 4169-007 Porto, Portugal
María Ángeles Abengózar, Centro de Investigaciones Biológicas (CSIC), Ramiro de Maeztu 9, 28040 Madrid, Spain
María Fernández-Reyes, Centro de Investigaciones Biológicas (CSIC), Ramiro de Maeztu 9, 28040 Madrid, Spain
David Andreu, Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Dr. Aguilar 88, 08003 Barcelona, Spain
Kamran Nazmi, Department of Oral Biochemistry, Academic Center for Dentistry Amsterdam (ACTA), University of Amsterdam and VU University Amsterdam, Gustav Mahlerlaan 3004, 1081 LA Amsterdam, The Netherlands
Jan G. M. Bolscher, Department of Oral Biochemistry, Academic Center for Dentistry Amsterdam (ACTA), University of Amsterdam and VU University Amsterdam, Gustav Mahlerlaan 3004, 1081 LA Amsterdam, The Netherlands
Margarida Bastos, Departamento de Química e Bioquímica, Faculdade de Ciências, Centro Investigação em Química CIQ(UP), Universidade do Porto, Rua do Campo Alegre, 4169-007 Porto, Portugal
Luis Rivas, Centro de Investigaciones Biológicas (CSIC), Ramiro de Maeztu 9, 28040 Madrid, Spain
Rapeseed (Brassica napus L.), which is the third leading source of vegetable oil, is sensitive to drought stress during the early vegetative growth
stage. To investigate the initial response of rapeseed to drought stress, changes in the protein expression profiles of drought-sensitive
(RGS-003) and drought-tolerant lines (SLM-003), and their F1 hybrid, were analyzed using a proteomics approach. Seven-day-old
rapeseed seedlings were treated with drought stress by restricting water for 7 days, and proteins were extracted from roots
and separated by two-dimensional polyacrylamide gel electrophoresis. In the sensitive rapeseed line, 35 protein spots were
differentially expressed under drought stress, and proteins related to metabolism, energy, disease/defense, and transport
were decreased. In the tolerant line, 32 protein spots were differentially expressed under drought stress, and proteins involved
in metabolism, disease/defense, and transport were increased, while energy-related proteins were decreased. Six protein spots
in F1 hybrid were common among expressed proteins in the drought-sensitive and -tolerant lines. Notably, tubulin beta-2 and
heat shock protein 70 were decreased in the drought-sensitive line and hybrid F1 plants, while jasmonate-inducible protein
and 20S proteasome subunit PAF1 were increased in the F1 hybrids and drought-tolerant line. These results indicate that (1)
V-type H+ ATPase, plasma-membrane associated cation-binding protein, HSP 90, and elongation factor EF-2 have a role in the drought
tolerance of rapeseed; (2) The decreased levels of heat shock protein 70 and tubulin beta-2 in the drought-sensitive and hybrid
F1 lines might explain the reduced growth of these lines in drought conditions.
Content Type Journal Article
Category Original Article
Pages 1-16
DOI 10.1007/s00726-012-1299-6
Authors
Payam Pour Mohammadi, National Institute of Crop Science, 2-1-18 Kannondai, Tsukuba, 305-8518 Japan
Ahmad Moieni, Faculty of Agriculture, Department of Biotechnology and Plant Breeding, Tarbiat Modares University, 14115-111 Tehran, Iran
Setsuko Komatsu, National Institute of Crop Science, 2-1-18 Kannondai, Tsukuba, 305-8518 Japan
Lactation is associated with elevated catabolism of branched-chain amino acids (BCAA) in mammary glands to produce glutamate,
glutamine, alanine, aspartate, and asparagine. This study determined effects of metabolic fuels on the catabolism of leucine
(a representative BCAA) in bovine mammary epithelial cells. Cells were incubated at 37 °C for 2 h in Krebs buffer containing
0.5 mM l-leucine and either l-[1-14C]leucine or l-[U-14C]leucine. The medium also contained 0–5 mM d-glucose, 0–2 mM l-glutamine, 0–4 mM dl-?-hydroxybutyrate, or 0–2 mM oleic acid. Rates of leucine decarboxylation were 60 % lower, but rates of ?-ketoisocaproate
production were 34 % higher, in the presence of 2 mM glucose than in its absence. All variables of leucine catabolism did
not differ between 2 and 5 mM glucose or between 0 and 4 mM dl-?-hydroxybutyrate. Compared with 0–0.25 mM glutamine, 0.5 and 2 mM l-glutamine reduced leucine transport, transamination, and decarboxylation. In contrast, increasing the concentration of oleic
acid from 0 to 2 mM dose-dependently stimulated leucine transamination, decarboxylation, and oxidation of carbons 2–6. Oleic
acid also enhanced the abundance of cytosolic BCAA transaminase, while reducing the phosphorylated level (inactive state)
of the E1? subunit of the mitochondrial branched-chain ?-ketoacid dehydrogenase complex. Thus, hypoglycemia or ketosis in
early lactation does not likely affect BCAA metabolism in mammary epithelial cells. Increasing circulating levels of BCAA
and oleic acid may have great potential to increase the syntheses of glutamate, glutamine, aspartate, alanine, and asparagine
by lactating mammary glands, thereby leading to enhanced production of milk for suckling neonates.
Content Type Journal Article
Category Original Article
Pages 1-11
DOI 10.1007/s00726-012-1302-2
Authors
Jian Lei, College of Animal Science, South China Agricultural University, Guangzhou, 510642 People’s Republic of China
Dingyuan Feng, College of Animal Science, South China Agricultural University, Guangzhou, 510642 People’s Republic of China
Yongliang Zhang, College of Animal Science, South China Agricultural University, Guangzhou, 510642 People’s Republic of China
Sudath Dahanayaka, Department of Animal Science and Faculty of Nutrition, Texas A&M University, College Station, TX 77843, USA
Xilong Li, Department of Animal Science and Faculty of Nutrition, Texas A&M University, College Station, TX 77843, USA
Kang Yao, Department of Animal Science and Faculty of Nutrition, Texas A&M University, College Station, TX 77843, USA
Junjun Wang, Department of Animal Science and Faculty of Nutrition, Texas A&M University, College Station, TX 77843, USA
Zhenlong Wu, State Key Laboratory of Animal Nutrition, China Agricultural University, Beijing, 100193 China
Zhaolai Dai, State Key Laboratory of Animal Nutrition, China Agricultural University, Beijing, 100193 China
Guoyao Wu, College of Animal Science, South China Agricultural University, Guangzhou, 510642 People’s Republic of China
This study determined whether N-acetylcysteine (NAC) could affect intestinal redox status, proinflammatory cytokines, epidermal growth factor (EGF), EGF
receptor (EGFR), Toll-like receptor-4 (TLR4), and aquaporin-8 in a lipopolysaccharide (LPS)-challenged piglet model. Eighteen
piglets (35-day-old) were randomly allocated into one of the three treatments (control, LPS and NAC). The control and LPS
groups were fed a basal diet, and the NAC group received the basal diet +500 mg/kg NAC. On days 10, 13, and 20 of the trial,
the LPS- and NAC-treated piglets received intraperitoneal administration of LPS (100 ?g/kg BW), whereas the control group
received the same volume of saline. On days 10 and 20, venous blood samples were obtained at 3 h post LPS or saline injection.
On day 21 of the trial, piglets were killed to obtain the intestinal mucosa for analysis. Compared with the control group,
LPS challenge reduced (P < 0.05) the activities of superoxide dismutase, catalase, and glutathione peroxidase in jejunal mucosae, while increasing
(P < 0.05) the concentrations of malondialdehyde, H2O2, O2·? and the ratio of oxidized to reduced glutathione in jejunal mucosae, and concentrations of TNF-?, cortisol, interleukin-6,
and prostaglandin E2 in both plasma and intestinal mucosae. These adverse effects of LPS were attenuated (P < 0.05) by NAC supplementation. Moreover, NAC prevented LPS-induced increases in abundances of intestinal HSP70 and NF-?B
p65 proteins and TLR4 mRNA. NAC supplementation enhanced plasma EGF concentration and intestinal EGFR mRNA levels. Collectively,
these results indicate that dietary NAC supplementation alleviates LPS-induced intestinal inflammation via regulating redox,
EGF, and TLR4 signaling.
Content Type Journal Article
Category Original Article
Pages 1-10
DOI 10.1007/s00726-012-1295-x
Authors
Yongqing Hou, Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, 430023 Wuhan, China
Lei Wang, Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, 430023 Wuhan, China
Dan Yi, Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, 430023 Wuhan, China
Binying Ding, Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, 430023 Wuhan, China
Zhenguo Yang, Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, 430023 Wuhan, China
Jiao Li, Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, 430023 Wuhan, China
Xing Chen, Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, 430023 Wuhan, China
Yinsheng Qiu, Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, 430023 Wuhan, China
Guoyao Wu, State Key Laboratory of Animal Nutrition, China Agricultural University, 100193 Beijing, China
Apelin receptor (APJ) deficiency has been reported to be preventive against atherosclerosis. However, the mechanism of this
effect remains unknown. In this study, quantitative real-time RT-PCR, Western blotting and ELISA analyses revealed a significant
increase in the expression of intercellular adhesion molecule-1(ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and monocyte
chemoattractant protein-1 (MCP-1) in human umbilical vein endothelial cells (HUVECs) treated with apelin. Inhibitors of cellular
signal transduction molecules were used to demonstrate involvement of nuclear factor kappa-B (NF-?B) and c-Jun N-terminal
kinase (JNK) pathways in apelin–APJ-induced activation of adhesion molecules and chemokines. Inhibition of APJ expression
by RNA interference abrogated apelin-induced expression of adhesion molecules and chemokines and apelin-stimulated cellular
signal transduction in HUVECs. The apelin–APJ system in endothelial cells is involved in the expression of adhesion molecules
and chemokines, which are important for the initiation of endothelial inflammation-related atherosclerosis. Therefore, apelin–APJ
and the cell signaling pathways activated by this system in endothelial cells may represent targets for therapy of atherosclerosis.
Content Type Journal Article
Category Original Article
Pages 1-12
DOI 10.1007/s00726-012-1298-7
Authors
Ying Lu, Department of Endocrinology, People’s Hospital of Zhongshan City, Zhongshan, Guangdong 528403, People’s Republic of China
Xiao Zhu, Institute of Metabolism and Endocrinology, The Second Xiang-Ya Hospital, Central South University, Changsha, Hunan 410011, People’s Republic of China
Gan-Xiong Liang, Department of Endocrinology, People’s Hospital of Zhongshan City, Zhongshan, Guangdong 528403, People’s Republic of China
Rong-Rong Cui, Institute of Metabolism and Endocrinology, The Second Xiang-Ya Hospital, Central South University, Changsha, Hunan 410011, People’s Republic of China
Yuan Liu, Institute of Metabolism and Endocrinology, The Second Xiang-Ya Hospital, Central South University, Changsha, Hunan 410011, People’s Republic of China
Shan-Shan Wu, Institute of Metabolism and Endocrinology, The Second Xiang-Ya Hospital, Central South University, Changsha, Hunan 410011, People’s Republic of China
Qiu-Hua Liang, Institute of Metabolism and Endocrinology, The Second Xiang-Ya Hospital, Central South University, Changsha, Hunan 410011, People’s Republic of China
Guan-Ying Liu, Institute of Metabolism and Endocrinology, The Second Xiang-Ya Hospital, Central South University, Changsha, Hunan 410011, People’s Republic of China
Yi Jiang, Institute of Metabolism and Endocrinology, The Second Xiang-Ya Hospital, Central South University, Changsha, Hunan 410011, People’s Republic of China
Xiao-Bo Liao, Department of Cardiothoracic Surgery, The Second Xiangya Hospital, Central South University, 139 Middle Renmin Road, Changsha, Hunan 410011, People’s Republic of China
Hui Xie, Institute of Metabolism and Endocrinology, The Second Xiang-Ya Hospital, Central South University, Changsha, Hunan 410011, People’s Republic of China
Hou-De Zhou, Institute of Metabolism and Endocrinology, The Second Xiang-Ya Hospital, Central South University, Changsha, Hunan 410011, People’s Republic of China
Xian-Ping Wu, Institute of Metabolism and Endocrinology, The Second Xiang-Ya Hospital, Central South University, Changsha, Hunan 410011, People’s Republic of China
Ling-Qing Yuan, Institute of Metabolism and Endocrinology, The Second Xiang-Ya Hospital, Central South University, Changsha, Hunan 410011, People’s Republic of China
Er-Yuan Liao, Institute of Metabolism and Endocrinology, The Second Xiang-Ya Hospital, Central South University, Changsha, Hunan 410011, People’s Republic of China
Taurine, 2-aminoethylsulfonic acid, is one of the most abundant amino acids in the brain. It has various important physiological
functions as a neuromodulator and antioxidant. Taurine is expected to be involved in depression; however, knowledge regarding
its function in relation to depression is limited. In this study, we attempted to elucidate the effects of oral taurine administration
on antidepressant-like behaviors in rats and depression-related signal transduction in the hippocampus. In behavioral tests,
rats fed a high taurine (HT: 45.0 mmol/kg taurine) diet for 4 weeks (HT4w) showed decreased immobility in the forced swim
test (FS) compared to controls. However, rats fed a low taurine (LT: 22.5 mmol/kg taurine) diet for 4 weeks or an HT diet
for 2 weeks (HT2w) did not show a significant difference in FS compared to controls. In biochemical analyses, the expression
of glutamic acid decarboxylase (GAD) 65 and GAD67 in the hippocampus was not affected by taurine administration. However,
the phosphorylation levels of extracellular signal-regulated kinase1/2 (ERK1/2), protein kinase B (Akt), glycogen synthase
kinase3 beta (GSK3?) and cAMP response element-binding protein (CREB) were increased in the hippocampus of HT4w and HT2w rats.
Phospho-calcium/calmodulin-dependent protein kinase II (CaMKII) was increased in the hippocampus of HT4w rats only. Moreover,
no significant changes in these molecules were observed in the hippocampus of rats fed an HT diet for 1 day. In conclusion,
our findings suggest that taurine has an antidepressant-like effect and an ability to change depression-related signaling
cascades in the hippocampus.
Content Type Journal Article
Category Original Article
Pages 1-10
DOI 10.1007/s00726-012-1282-2
Authors
Wataru Iio, College of Agriculture, Ibaraki University, Ami, Ibaraki 300-0393, Japan
Noriko Matsukawa, Kyoto Institute of Nutrition and Pathology Inc., Ujitawara, Kyoto 610-0231, Japan
Takamitsu Tsukahara, Kyoto Institute of Nutrition and Pathology Inc., Ujitawara, Kyoto 610-0231, Japan
Atsushi Toyoda, College of Agriculture, Ibaraki University, Ami, Ibaraki 300-0393, Japan
Molecularly imprinted polymers (MIP) for histamine using methacrylic acid were developed and recognition mechanisms were thoroughly
characterized for the first time in this study. The binding affinity of imprinted polymer with structurally related compounds
was studied in organic and aqueous media, at various conditions. In organic media, MIP was found to bind histamine two and
six times more than ranitidine and fluoxetine, respectively, whereas higher selectivity was observed in the case of dimentidene
or disodium cromoglycate. The specific binding sites of MIP recognized histamine over l-histidine in aqueous conditions, while higher affinity for histamine compared to ranitidine, disodium cromoglycate, putrescine
and to a putrescine analogue was observed. A combination of NMR and UV spectroscopy analyses for investigation of imprinting
and recognition properties revealed that strong specific interactions between the functional monomer and histamine in the
prepolymerization and in the aqueous solutions were probably responsible for histamine recognition. The preparation of histamine
MIPs and elucidation of imprinting and recognition mechanism may serve as useful insight for future application of MIPs.
Content Type Journal Article
Category Original Article
Pages 1-12
DOI 10.1007/s00726-012-1297-8
Authors
Foteini A. Trikka, Laboratory of Biochemistry, Department of Chemistry, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece
Keiichi Yoshimatsu, Pure and Applied Biochemistry, Chemical Center, Lund University, Box 124, 221 00 Lund, Sweden
Lei Ye, Pure and Applied Biochemistry, Chemical Center, Lund University, Box 124, 221 00 Lund, Sweden
Dimitrios A. Kyriakidis, Laboratory of Biochemistry, Department of Chemistry, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece
While abnormalities in monoamine metabolism have been investigated heavily per potential roles in the mechanisms of depression,
the contribution of amino acid metabolism in the brain remains not well understood. In additional, roles of the hypothalamus–pituitary–adrenal
axis in stress-regulation mechanisms have been of much focus, while the contribution of central amino acid metabolism to these
mechanisms has not been well appreciated. Therefore, whether depression-like states affect amino acid metabolism and their
potential roles on stress-regulatory mechanisms were investigated by comparing Wistar Kyoto rats, which display depression-like
behaviors and stress vulnerability, to control Wistar rats. Brain amino acid metabolism in Wistar Kyoto rats was greatly different
from normal Wistar rats, with special reference to lower cystathionine and serine levels. In addition, Wistar Kyoto rats demonstrated
abnormality in dopamine metabolism compared with Wistar rats. In the case of stress response, amino acid levels having a sedative
and/or hypnotic effect were constant in the brain of Wistar Kyoto rats, though these amino acid levels were reduced in Wistar
rats under a stressful condition. These results suggest that the abnormal amino acid metabolism may induce depression-like
behaviors and stress vulnerability in Wistar Kyoto rats. Therefore, we hypothesized that abnormalities in amino acid and monoamine
metabolism may induce depression, and amino acid metabolism in the brain may be related to stress vulnerability.
Content Type Journal Article
Category Original Article
Pages 1-11
DOI 10.1007/s00726-012-1294-y
Authors
Mao Nagasawa, Laboratory of Regulation in Metabolism and Behavior, Graduate School of Bioresource and Bioenvironmental Sciences, Kyushu University, Fukuoka, 812-8581 Japan
Yumi Ogino, Laboratory of Regulation in Metabolism and Behavior, Graduate School of Bioresource and Bioenvironmental Sciences, Kyushu University, Fukuoka, 812-8581 Japan
Koji Kurata, Laboratory of Regulation in Metabolism and Behavior, Graduate School of Bioresource and Bioenvironmental Sciences, Kyushu University, Fukuoka, 812-8581 Japan
Tsuyoshi Otsuka, Laboratory of Regulation in Metabolism and Behavior, Graduate School of Bioresource and Bioenvironmental Sciences, Kyushu University, Fukuoka, 812-8581 Japan
Jyunki Yoshida, Laboratory of Regulation in Metabolism and Behavior, Graduate School of Bioresource and Bioenvironmental Sciences, Kyushu University, Fukuoka, 812-8581 Japan
Shozo Tomonaga, Laboratory of Regulation in Metabolism and Behavior, Graduate School of Bioresource and Bioenvironmental Sciences, Kyushu University, Fukuoka, 812-8581 Japan
Mitsuhiro Furuse, Laboratory of Regulation in Metabolism and Behavior, Graduate School of Bioresource and Bioenvironmental Sciences, Kyushu University, Fukuoka, 812-8581 Japan
Enediyne–peptide conjugates were designed with the aim to inhibit aminopeptidase N, a widespread ectoenzyme with a variety
of functions, like protein digestion, inactivation of cytokines in the immune system and endogenous opioid peptides in the
central nervous system. Enediyne moiety was embedded within the 12-membered ring with hydrophobic amino acid alanine, valine,
leucine or phenylalanine used as carriers. Aromatic part of the enediyne bridging unit and the amino acid side chains were
considered as pharmacophores for the binding to the aminopeptidase N (APN) active site. Additionally, the fused enediyne–amino
acid “heads” were bound through a flexible linker to the l-lysine, an amino group donor. The synthesis included building the aromatic enediyne core at the C-terminal of amino acids
and subsequent intramolecular N-alkylation. APN inhibition test revealed that the alanine-based derivative 9a inhibits the APN with IC50 of 34 ± 11 ?M. Enediyne–alanine conjugate 12 missing the flexible linker was much less effective in the APN inhibition. These results show that enediyne-fused amino acids
have potential as new pharmacophores in the design of APN inhibitors.
Content Type Journal Article
Category Original Article
Pages 1-14
DOI 10.1007/s00726-012-1292-0
Authors
Matija Gredi?ak, Division of Organic Chemistry and Biochemistry, Ru?er Boškovi? Institute, Bijeni?ka cesta 54, HR-10002 Zagreb, Croatia
Marija Abrami?, Division of Organic Chemistry and Biochemistry, Ru?er Boškovi? Institute, Bijeni?ka cesta 54, HR-10002 Zagreb, Croatia
Ivanka Jeri?, Division of Organic Chemistry and Biochemistry, Ru?er Boškovi? Institute, Bijeni?ka cesta 54, HR-10002 Zagreb, Croatia
Glutamate is one of the most abundant of the amino acids. In addition to its role in protein structure, it plays critical
roles in nutrition, metabolism and signaling. Post-translational carboxylation of glutamyl residues increases their affinity
for calcium and plays a major role in hemostasis. Glutamate is of fundamental importance to amino acid metabolism, yet the
great bulk of dietary glutamate is catabolyzed within the intestine. It is necessary for the synthesis of key molecules, such
as glutathione and the polyglutamated folate cofactors. It plays a major role in signaling. Within the central nervous system,
glutamate is the major excitatory neurotransmitter and its product, GABA, the major inhibitory neurotransmitter. Glutamate
interaction with specific taste cells in the tongue is a major component of umami taste. The finding of glutamate receptors
throughout the gastrointestinal tract has opened up a new vista in glutamate function. Glutamate is truly a functional amino
acid.
Content Type Journal Article
Category Review Article
Pages 1-6
DOI 10.1007/s00726-012-1280-4
Authors
John T. Brosnan, Department of Biochemistry, Memorial University of Newfoundland, St. John’s, NL A1B 3X9, Canada
Margaret E. Brosnan, Department of Biochemistry, Memorial University of Newfoundland, St. John’s, NL A1B 3X9, Canada
?-Aminoxy peptide AxyP1 has been reported to form synthetic chloride channel in living cells, thus it may have therapeutic
potential for the treatment of diseases associated with chloride channel dysfunction. However, this study revealed significant
gastrointestinal (GI) instability and extensive hepatic metabolism of AxyP1. To improve its GI and metabolic stability, structural
modifications were conducted by replacing the isobutyl side chains of AxyP1 with methyl group (AxyP2), hydroxymethyl group
(AxyP3), 4-aminobutyl group (AxyP4) and 3-carboxyl propyl group (AxyP5). Compared with AxyP1 (41 and 47 % degradation), GI
stability of the modified peptides was significantly improved by 8-fold (AxyP2), 9-fold (AxyP3) and 12-fold (AxyP5) with no
degradation for AxyP4 in simulated gastric fluid within 1 h, and by 12-fold (AxyP2) and 9-fold (AxyP3) with no degradation
for AxyP4 and AxyP5 in simulated intestinal fluid within 3 h, respectively. The hepatic metabolic stability of the four modified
peptides within 30 min in rat liver S9 preparation was also improved significantly with no metabolism of AxyP5 and threefold
(AxyP2 and AxyP4) and eightfold (AxyP3) less metabolism compared with AxyP1 (39 % metabolism). Unlike hydrolysis as the major
metabolism of peptides of natural ?-amino acids, oxidation mediated by the cytochrome P450 enzymes, especially CYP3A subfamily,
to form the corresponding mono-hydroxyl metabolites was the predominant hepatic metabolism of the five ?-aminoxy peptides
tested. The present findings demonstrate that structural modification can significantly improve the GI and metabolic stability
of ?-aminoxy peptides and thus increase their potential for therapeutic use in the treatment of chloride channel related diseases.
Content Type Journal Article
Category Original Article
Pages 1-13
DOI 10.1007/s00726-012-1291-1
Authors
Bin Ma, School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong SAR, People’s Republic of China
Chun Yin, School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong SAR, People’s Republic of China
Dan Yang, Department of Chemistry, The University of Hong Kong, Hong Kong SAR, People’s Republic of China
Ge Lin, School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong SAR, People’s Republic of China
The impact of inserting hydrocarbon staples into short ?-helical antimicrobial peptides lasioglossin III and melectin (antimicrobial
peptides of wild bee venom) on their biological and biophysical properties has been examined. The stapling was achieved by
ring-closing olefin metathesis, either between two S-2-(4?-pentenyl) alanine residues (S5) incorporated at i and i + 4 positions or between R-2-(7?-octenyl) alanine (R8) and S5 incorporated at the i and i + 7 positions, respectively. We prepared several lasioglossin III and melectin analogs with a single staple inserted into
different positions within the peptide chains as well as analogs with double staples. The stapled peptides exhibited a remarkable
increase in hemolytic activity, while their antimicrobial activities decreased. Some single stapled peptides showed a higher
resistance against proteolytic degradation than native ones, while the double stapled analogs were substantially more resistant.
The CD spectra of the singly stapled peptides measured in water showed only a slightly better propensity to form ?-helical
structure when compared to native peptides, whereas the doubly stapled analogs exhibited dramatically enhanced ?-helicity.
Content Type Journal Article
Category Original Article
Pages 1-12
DOI 10.1007/s00726-012-1283-1
Authors
Hubert Chapuis, Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo 2, Prague 6, 16610 Czech Republic
Ji?ina Slaninová, Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo 2, Prague 6, 16610 Czech Republic
Lucie Bednárová, Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo 2, Prague 6, 16610 Czech Republic
Lenka Monincová, Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo 2, Prague 6, 16610 Czech Republic
Miloš Bud?šínský, Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo 2, Prague 6, 16610 Czech Republic
Václav ?e?ovský, Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo 2, Prague 6, 16610 Czech Republic
Zebrafish form shoals in nature and in the laboratory. The sight of conspecifics has been found reinforcing in zebrafish learning
tasks. However, the mechanisms of shoaling, and those of its reinforcing properties, are not known. The dopaminergic system
has been implicated in reward among other functions and it is also engaged by drugs of abuse as shown in a variety of vertebrates
including zebrafish. The ontogenetic changes in dopamine levels and, to a lesser degree, in serotonin levels, have been found
to accompany the maturation of shoaling in zebrafish. Thus, we hypothesized that the dopaminergic system may contribute to
shoaling in zebrafish. To test this we employed a D1-receptor antagonist and quantified behavioral responses of our subjects
using a social preference (shoaling) paradigm. We found significant reduction of social preference induced by the D1-R antagonist,
SCH23390, in the AB strain of zebrafish, an alteration that was not accompanied by changes in motor function or vision. We
also detected D1-R antagonist-induced changes in the level of dopamine, DOPAC, serotonin and 5HIAA, respectively, in the brain
of AB zebrafish as quantified by HPLC with electrochemical detection. We found the antagonist-induced behavioral changes to
be absent and the levels of these neurochemicals to be lower in another zebrafish population, SF, demonstrating naturally
occurring genetic variability in these traits. We conclude that this variability may be utilized to unravel the mechanisms
of social behavior in zebrafish, a line of research that may be extended to other vertebrates including our own species.
Content Type Journal Article
Category Original Article
Pages 1-14
DOI 10.1007/s00726-012-1284-0
Authors
Tanya Scerbina, Department of Psychology, University of Toronto Mississauga, 3359 Mississauga Road North, Rm 4020C, Mississauga, ON L5L 1C6, Canada
Diptendu Chatterjee, Department of Psychology, University of Toronto Mississauga, 3359 Mississauga Road North, Rm 4020C, Mississauga, ON L5L 1C6, Canada
Robert Gerlai, Department of Psychology, University of Toronto Mississauga, 3359 Mississauga Road North, Rm 4020C, Mississauga, ON L5L 1C6, Canada
In this paper, adsorption behaviors of typical neutral (alanine), acidic (glutamic acid) and basic (lysine) amino acids onto
the surfaces of neutral as well as positively and negatively charged silver chloride nanoparticles were examined. Silver chloride
nanoparticles with different charges and different water content were synthesized by reverse micelle method. The adsorptions
of the above mentioned amino acids onto the surfaces of differently charged silver chloride nanoparticles were found to depend
strongly on various parameters including pH of the aqueous solution, type of amino acid, water to surfactant mole ratio, and
type of charges on the surfaces of silver chloride nanoparticles. It was found that the interaction of –NH3+ groups of the amino acids with silver ion could be a driving force for adsorption of amino acids. Alanine and Glutamic acid
showed almost similar trend for being adsorbed on the surface of silver chloride nanoparticles. Electrostatic interaction,
hydrophobicity of both nanoparticle and amino acid, complex formation between amine group and silver ion, interaction between
protonated amine and silver ion as well as the number of nanoparticles per unit volume of solution were considered for interpreting
the observed results.
Content Type Journal Article
Category Original Article
Pages 1-13
DOI 10.1007/s00726-012-1270-6
Authors
Ghodratollah Absalan, Professor Massoumi Laboratory, Department of Chemistry, Faculty of Sciences, Shiraz University, 71457 Shiraz, Iran
Maryam Ghaemi, Professor Massoumi Laboratory, Department of Chemistry, Faculty of Sciences, Shiraz University, 71457 Shiraz, Iran
The lipopeptaibol trichogin GA IV is a natural, non-ribosomally synthesized, antimicrobial peptide remarkably resistant to
the action of hydrolytic enzymes. This feature may be connected to the multiple presence in its sequence of the non-coded
residue ?-aminoisobutyric acid (Aib), which is known to be responsible for the adoption of particularly stable helical structures
already at the level of short peptides. To investigate the role of Aib residues on the 3D-structure and bioactivity of trichogin
GA IV, we synthesized and fully characterized four analogs where one or two Aib residues are replaced by l-Leu. Our extensive conformational studies (including an X-ray diffraction analysis) and biological assays performed on these
analogs showed that the Aib to l-Leu replacements do not affect the resistance to proteolysis, but modulate the bioactivity of trichogin GA IV in a 3D-structure
related manner.
Content Type Journal Article
Category Original Article
Pages 1-17
DOI 10.1007/s00726-012-1261-7
Authors
Marta De Zotti, ICB, Padova Unit, CNR, Department of Chemistry, University of Padova, 35131 Padova, Italy
Barbara Biondi, ICB, Padova Unit, CNR, Department of Chemistry, University of Padova, 35131 Padova, Italy
Yoonkyung Park, Department of Biotechnology, Chosun University, 501-759 Gwangju, Korea
Kyung-Soo Hahm, Department of Cellular Molecular Medicine, School of Medicine, Chosun University, 501-759 Gwangju, Korea
Marco Crisma, ICB, Padova Unit, CNR, Department of Chemistry, University of Padova, 35131 Padova, Italy
Claudio Toniolo, ICB, Padova Unit, CNR, Department of Chemistry, University of Padova, 35131 Padova, Italy
Fernando Formaggio, ICB, Padova Unit, CNR, Department of Chemistry, University of Padova, 35131 Padova, Italy
An expedient chemical synthesis of a 75mer peptide corresponding to the DNA binding domain (DBD, 227–301) of the human MafA
leucine zipper transcription factor is reported. The application of microwave-assisted solid phase peptide synthesis (MW-SPPS)
with a protocol modified respect to the standard one allowed obtaining the desired 75mer peptide in a short time with high
quantity and optimal purity. MW-SPPS methodology was thus demonstrated as a valuable alternative to recombinant methods to
obtain protein domains. Considering that recent findings suggest an involvement of MafA in the pathogenesis of diabetes mellitus,
we also performed circular dichroism studies both on DBD folding and its interaction with MafA recognition element (MARE)
on insulin enhancer. From our results, it was evicted that a disorder to order transition occurs after DBD interaction with
insulin MARE which is mediated by specific structural elements on the N-terminus of the DBD.
Content Type Journal Article
Category Original Article
Pages 1-9
DOI 10.1007/s00726-012-1274-2
Authors
Sara Pellegrino, Dipartimento di Scienze Molecolari Applicate ai Biosistemi, Sezione Chimica Organica “A. Marchesini”, Università degli Studi di Milano, via Venezian 21, 20133 Milan, Italy
Chiara Annoni, Dipartimento di Scienze Molecolari Applicate ai Biosistemi, Sezione Chimica Organica “A. Marchesini”, Università degli Studi di Milano, via Venezian 21, 20133 Milan, Italy
Alessandro Contini, Dipartimento di Scienze Molecolari Applicate ai Biosistemi, Sezione Chimica Organica “A. Marchesini”, Università degli Studi di Milano, via Venezian 21, 20133 Milan, Italy
Francesca Clerici, Dipartimento di Scienze Molecolari Applicate ai Biosistemi, Sezione Chimica Organica “A. Marchesini”, Università degli Studi di Milano, via Venezian 21, 20133 Milan, Italy
Maria Luisa Gelmi, Dipartimento di Scienze Molecolari Applicate ai Biosistemi, Sezione Chimica Organica “A. Marchesini”, Università degli Studi di Milano, via Venezian 21, 20133 Milan, Italy
In 1970s, taurine deficiency was reported to induce photoreceptor degeneration in cats and rats. Recently, we found that taurine
deficiency contributes to the retinal toxicity of vigabatrin, an antiepileptic drug. However, in this toxicity, retinal ganglion
cells were degenerating in parallel to cone photoreceptors. The aim of this study was to re-assess a classic mouse model of
taurine deficiency following a treatment with guanidoethane sulfonate (GES), a taurine transporter inhibitor to determine
whether retinal ganglion cells are also affected. GES treatment induced a significant reduction in the taurine plasma levels
and a lower weight increase. At the functional level, photopic electroretinograms were reduced indicating a dysfunction in
the cone pathway. A change in the autofluorescence appearance of the eye fundus was explained on histological sections by
an increased autofluorescence of the retinal pigment epithelium. Although the general morphology of the retina was not affected,
cell damages were indicated by the general increase in glial fibrillary acidic protein expression. When cell quantification
was achieved on retinal sections, the number of outer/inner segments of cone photoreceptors was reduced (20 %) as the number
of retinal ganglion cells (19 %). An abnormal synaptic plasticity of rod bipolar cell dendrites was also observed in GES-treated
mice. These results indicate that taurine deficiency can not only lead to photoreceptor degeneration but also to retinal ganglion
cell loss. Cone photoreceptors and retinal ganglion cells appear as the most sensitive cells to taurine deficiency. These
results may explain the recent therapeutic interest of taurine in retinal degenerative pathologies.
Content Type Journal Article
Category Original Article
Pages 1-15
DOI 10.1007/s00726-012-1273-3
Authors
David Gaucher, INSERM, U-968, Insitut de la Vision Retinal Information Processing: Pharmacology and Pathologies, 17, rue Moreau, 75012 Paris, France
Emilie Arnault, INSERM, U-968, Insitut de la Vision Retinal Information Processing: Pharmacology and Pathologies, 17, rue Moreau, 75012 Paris, France
Zoé Husson, INSERM, U-968, Insitut de la Vision Retinal Information Processing: Pharmacology and Pathologies, 17, rue Moreau, 75012 Paris, France
Nicolas Froger, INSERM, U-968, Insitut de la Vision Retinal Information Processing: Pharmacology and Pathologies, 17, rue Moreau, 75012 Paris, France
Elisabeth Dubus, INSERM, U-968, Insitut de la Vision Retinal Information Processing: Pharmacology and Pathologies, 17, rue Moreau, 75012 Paris, France
Pauline Gondouin, INSERM, U-968, Insitut de la Vision Retinal Information Processing: Pharmacology and Pathologies, 17, rue Moreau, 75012 Paris, France
Diane Dherbécourt, INSERM, U-968, Insitut de la Vision Retinal Information Processing: Pharmacology and Pathologies, 17, rue Moreau, 75012 Paris, France
Julie Degardin, INSERM, U-968, Insitut de la Vision Retinal Information Processing: Pharmacology and Pathologies, 17, rue Moreau, 75012 Paris, France
Manuel Simonutti, INSERM, U-968, Insitut de la Vision Retinal Information Processing: Pharmacology and Pathologies, 17, rue Moreau, 75012 Paris, France
Stéphane Fouquet, INSERM, U-968, Insitut de la Vision Retinal Information Processing: Pharmacology and Pathologies, 17, rue Moreau, 75012 Paris, France
M. A. Benahmed, Université de Strasbourg, UMR7237, Strasbourg, France
K. Elbayed, Université de Strasbourg, UMR7177, Strasbourg, France
Izzie-Jacques Namer, Université de Strasbourg, UMR7237, Strasbourg, France
Pascale Massin, Hôpital Lariboisière, Paris, France
José-Alain Sahel, INSERM, U-968, Insitut de la Vision Retinal Information Processing: Pharmacology and Pathologies, 17, rue Moreau, 75012 Paris, France
Serge Picaud, INSERM, U-968, Insitut de la Vision Retinal Information Processing: Pharmacology and Pathologies, 17, rue Moreau, 75012 Paris, France
Ezrin-radixin-moesin-binding phosphoprotein-50 (EBP50) suppresses breast cancer cell proliferation, potentially through its
regulatory effect on epidermal growth factor receptor (EGFR) signaling, although the mechanism by which this occurs remains
unknown. Thus in our studies, we aimed to determine the effect of EBP50 expression on EGF-induced cell proliferation and activation
of EGFR signaling in the breast cancer cell lines, MDA-MB-231 and MCF-7. In MDA-MB-231 cells, which express low levels of
EBP50, EBP50 overexpression inhibited EGF-induced cell proliferation, ERK1/2 and AKT phosphorylation. In MCF-7 cells, which
express high levels of EBP50, EBP50 knockdown promoted EGF-induced cell proliferation, ERK1/2 and AKT phosphorylation. Knockdown
of EBP50 in EBP50-overexpressed MDA-MB-231 cells abrogated the inhibitory effect of EBP50 on EGF-stimulated ERK1/2 phosphorylation
and restoration of EBP50 expression in EBP50-knockdown MCF-7 cells rescued the inhibition of EBP50 on EGF-stimulated ERK1/2
phosphorylation, further confirming that the activation of EGF-induced downstream molecules could be specifically inhibited
by EBP50 expression. Since EGFR signaling was triggered by EGF ligands via EGFR phosphorylation, we further detected the phosphorylation
status of EGFR in the presence or absence of EBP50 expression. Overexpression of EBP50 in MDA-MB-231 cells inhibited EGF-stimulated
EGFR phosphorylation, whereas knockdown of EBP50 in MCF-7 cells enhanced EGF-stimulated EGFR phosphorylation. Meanwhile, total
expression levels of EGFR were unaffected during EGF stimulation. Taken together, our data shows that EBP50 can suppress EGF-induced
proliferation of breast cancer cells by inhibiting EGFR phosphorylation and blocking EGFR downstream signaling in breast cancer
cells. These results provide further insight into the molecular mechanism by which EBP50 regulates the development and progression
of breast cancer.
Content Type Journal Article
Category Original Article
Pages 1-9
DOI 10.1007/s00726-012-1277-z
Authors
Wenfang Yao, Department of Biochemistry and Molecular Biology, Capital Medical University, Beijing, 100069 People’s Republic of China
Duiping Feng, Department of Biochemistry and Molecular Biology, Capital Medical University, Beijing, 100069 People’s Republic of China
Weihua Bian, Department of Biochemistry and Molecular Biology, Capital Medical University, Beijing, 100069 People’s Republic of China
Longyan Yang, Department of Biochemistry and Molecular Biology, Capital Medical University, Beijing, 100069 People’s Republic of China
Yang Li, Department of Biochemistry and Molecular Biology, Capital Medical University, Beijing, 100069 People’s Republic of China
Zhiyu Yang, Department of Biochemistry and Molecular Biology, Capital Medical University, Beijing, 100069 People’s Republic of China
Ying Xiong, Department of Biochemistry and Molecular Biology, Capital Medical University, Beijing, 100069 People’s Republic of China
Junfang Zheng, Department of Biochemistry and Molecular Biology, Capital Medical University, Beijing, 100069 People’s Republic of China
Renyou Zhai, Department of Radiology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, 100020 People’s Republic of China
Junqi He, Department of Biochemistry and Molecular Biology, Capital Medical University, Beijing, 100069 People’s Republic of China
Intracerebroventricular (i.c.v.) administration of l-aspartate (l-Asp) attenuates stress responses in neonatal chicks, but the mechanism has not been clarified. In the present study, three
behavioral experiments were carried out under socially isolated stressful conditions exacerbated by the use of corticotrophin-releasing
factor (CRF). In Experiment 1, i.c.v. injection of l-Asp attenuated behavioral stress responses (distress vocalization and active wakefulness) in a dose-dependent manner. Furthermore,
l-Asp increased time spent standing/sitting motionless with eyes open and sitting motionless with head dropped (sleeping posture)
in comparison with the group receiving CRF alone. In Experiment 2, i.c.v. injection of d-Asp dose-dependently decreased the number of distress vocalizations and the amount of time spent in active wakefulness. d-Asp increased the time spent standing/sitting motionless with eyes open compared with the group receiving CRF alone. In Experiment
3, we directly compared the effect of l-Asp with that of d-Asp. Both l- and d-Asp induced sedative effects under an acutely stressful condition. However, l-Asp, but not d-Asp, increased the time spent in a sleeping posture. These results indicate that both l- and d-Asp, when present in the brain, could induce a sedative effect, while the mechanism for hypnosis in neonatal chicks may be
different for l-Asp in comparison with d-Asp.
Content Type Journal Article
Category Original Article
Pages 1-8
DOI 10.1007/s00726-012-1272-4
Authors
Edi Erwan, Laboratory of Regulation in Metabolism and Behavior, Faculty of Agriculture, Graduate School of Bioresource and Bioenvironmental Sciences, Kyushu University, Higashi-ku, Fukuoka, 812-8581 Japan
Shozo Tomonaga, Laboratory of Regulation in Metabolism and Behavior, Faculty of Agriculture, Graduate School of Bioresource and Bioenvironmental Sciences, Kyushu University, Higashi-ku, Fukuoka, 812-8581 Japan
Junki Yoshida, Laboratory of Regulation in Metabolism and Behavior, Faculty of Agriculture, Graduate School of Bioresource and Bioenvironmental Sciences, Kyushu University, Higashi-ku, Fukuoka, 812-8581 Japan
Mao Nagasawa, Laboratory of Regulation in Metabolism and Behavior, Faculty of Agriculture, Graduate School of Bioresource and Bioenvironmental Sciences, Kyushu University, Higashi-ku, Fukuoka, 812-8581 Japan
Yumi Ogino, Laboratory of Regulation in Metabolism and Behavior, Faculty of Agriculture, Graduate School of Bioresource and Bioenvironmental Sciences, Kyushu University, Higashi-ku, Fukuoka, 812-8581 Japan
D. Michael Denbow, Department of Animal and Poultry Sciences, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061-0306, USA
Mitsuhiro Furuse, Laboratory of Regulation in Metabolism and Behavior, Faculty of Agriculture, Graduate School of Bioresource and Bioenvironmental Sciences, Kyushu University, Higashi-ku, Fukuoka, 812-8581 Japan
To establish a system to study differentiation therapy drugs, we used the androgen-independent human prostate PC-3 tumor cell
line as a target and ?- and ?-tocopherol as inducers. Effects of ?- and ?-tocopherol on the cell cycle, proliferation and
differentiation, were examined. A more significant growth inhibition activity for ?- than for ?-tocopherol was observed. Flow
cytometry analysis of ?- and ?-tocopherol-treated prostate carcinoma PC3 cells showed decreased progression into the S-phase.
This effect, particularly evident for ?-tocopherol, was associated with an up-regulation and increased activity of transglutaminase
2 (TG2), a reduced DNA synthesis and a remarkable decreased levels of cyclin D1 and cyclin E. Activation of TG2 suggests that
?-tocopherol has an evident differentiative capacity on PC3 cells, leading to an increased expression of TG2, and reduced
cyclin D1 and cyclin E levels, affecting cell cycle progression. It is feasible that up-regulation and activation of TG2,
associated with a reduced proliferation, are parts of a large-scale reprogramming that can attenuate the malignant phenotype
of PC3 cells in vitro. These data suggest further investigation on the potential use of this ?-form of vitamin E as a differentiative
agent, in combination with the common cytotoxic treatments for prostate cancer therapy.
Content Type Journal Article
Category Original Article
Pages 1-7
DOI 10.1007/s00726-012-1278-y
Authors
P. Torricelli, Department SPES, University of Molise, Campobasso, Italy
M. Caraglia, Department of Biochemistry and Biophysics, Second University of Naples, Naples, Italy
A. Abbruzzese, Department of Biochemistry and Biophysics, Second University of Naples, Naples, Italy
S. Beninati, Department of Biology, University of Rome “Tor Vergata”, Rome, Italy
Chiral imines 1a,b, already synthesized in our laboratory, were converted in good yield by reduction into the corresponding N-benzyl-?-lactams 2a,b. Desilylation followed by oxidation of the hydroxymethyl functionality gave the N-benzyl-?-amino acids 5a,b in good yield and high purity. Starting from compound 6a, the corresponding ?-peptoid dimer 8 was prepared, together with its derivatives 9 and 10, these latter displaying conformational restriction about the peptide bond, as evidenced by NMR data.
Content Type Journal Article
Category Original Article
Pages 1-10
DOI 10.1007/s00726-012-1275-1
Authors
Gianluca Martelli, Di.S.V.A.-Chemistry, Polytechnic University of Marche, Via Brecce Bianche, 60131 Ancona, Italy
Antonella Monsignori, Di.S.V.A.-Chemistry, Polytechnic University of Marche, Via Brecce Bianche, 60131 Ancona, Italy
Mario Orena, Di.S.V.A.-Chemistry, Polytechnic University of Marche, Via Brecce Bianche, 60131 Ancona, Italy
Samuele Rinaldi, Di.S.V.A.-Chemistry, Polytechnic University of Marche, Via Brecce Bianche, 60131 Ancona, Italy
Nicola Castellucci, Department of Chemistry “G. Ciamician”, Alma Mater Studiorum University of Bologna, Via Selmi 2, 40126 Bologna, Italy
Claudia Tomasini, Department of Chemistry “G. Ciamician”, Alma Mater Studiorum University of Bologna, Via Selmi 2, 40126 Bologna, Italy
The application of carnosine in medicine has been discussed since several years, but many claims of therapeutic effects have
not been substantiated by rigorous experimental examination. In the present perspective, a possible use of carnosine as an
anti-neoplastic therapeutic, especially for the treatment of malignant brain tumours such as glioblastoma is discussed. Possible
mechanisms by which carnosine may perform its anti-tumourigenic effects are outlined and its expected bioavailability and
possible negative and positive side effects are considered. Finally, alternative strategies are examined such as treatment
with other dipeptides or ?-alanine.
Content Type Journal Article
Category Introduction
Pages 1-8
DOI 10.1007/s00726-012-1271-5
Authors
Frank Gaunitz, Klinik und Poliklinik für Neurochirurgie, Universitätsklinikum Leipzig AöR, 04103 Leipzig, Germany
Alan R. Hipkiss, Aston Research Centre for Healthy Ageing (ARCHA), School of Health and Life Sciences, Aston University, Birmingham, B4 7ET UK
This study presents a design of a highly potent and competitive inhibitory peptide for 3-hydroxy-3-methylglutaryl CoA reductase
(HMGR). HMGR is the major regulatory enzyme of cholesterol biosynthesis and the target enzyme of many investigations aimed
at lowering the rate of cholesterol biosynthesis. In previous studies, the two hypocholesterolemic peptides (LPYP and IAVPGEVA)
were isolated and identified from soy protein. Based on these peptide sequences, a number of peptides were designed previously
by using the correlation between the conformational flexibility and bioactivity. The design method that was applied in previous
studies was slightly modified for the purpose of the current research and 12 new peptides were designed and synthesized. Among
all peptides, SFGYVAE showed the highest ability to inhibit HMGR. A kinetic analysis revealed that this peptide is a competitive
inhibitor of HMG-CoA with an equilibrium constant of inhibitor binding (Ki) of 12 ± 0.4 nM. This is an overall 14,500-fold increase in inhibitory activity compared to the first isolated LPYP peptide
from soybeans. Conformational data support a conformation of the designed peptides close to the bioactive conformation of
the previously synthesized active peptides.
Content Type Journal Article
Category Original Article
Pages 1-11
DOI 10.1007/s00726-012-1276-0
Authors
Valeriy V. Pak, Department of Organic Synthesis, Institute of the Chemistry of Plant Substances, Building 77, Acad. Kh. Abdullaev Str., 100170 Tashkent, Uzbekistan
Minseon Koo, Food Fusion and Complex Research Division, Korea Food Research Institute, Baekhyun-Dong, Bundang-Ku, Songnam-Si, Kyongki-Do 463-746, Republic of Korea
Dae Young Kwon, Food Fusion and Complex Research Division, Korea Food Research Institute, Baekhyun-Dong, Bundang-Ku, Songnam-Si, Kyongki-Do 463-746, Republic of Korea
Lyubov Yun, Department of Organic Synthesis, Institute of the Chemistry of Plant Substances, Building 77, Acad. Kh. Abdullaev Str., 100170 Tashkent, Uzbekistan
Catabolism of amino acids (AA) by intestinal bacteria greatly affects their bioavailability in the systemic circulation and
the health of animals and humans. This study tests the novel hypothesis that l-glutamine regulates AA utilization by luminal bacteria of the small intestine. Pure bacterial strains (Streptococcus sp., Escherichia coli and Klebsiella sp.) and mixed bacterial cultures derived from the jejunum or ileum of pigs were cultured in the presence of 0–5 mM l-glutamine under anaerobic conditions. After 3 h of incubation, samples were taken for the determination of AA utilization.
Results showed concentration-dependent increases in the utilization of glutamine in parallel with the increased conversion
of glutamine into glutamate in all the bacteria. Complete utilization of asparagine, aspartate and serine was observed in
pure bacterial strains after the 3-h incubation. The addition of glutamine reduced the net utilization of asparagine by both
jejunal and ileal mixed bacteria. Net utilization of lysine, leucine, valine, ornithine and serine by jejunal or ileal mixed
bacteria decreased with the addition of glutamine in a concentration-dependent manner. Collectively, glutamine dynamically
modulates the bacterial metabolism of the arginine family of AA as well as the serine and aspartate families of AA and reduced
the catabolism of most AA (including nutritionally essential and nonessential AA) in jejunal or ileal mixed bacteria. The
beneficial effects of glutamine on gut nutrition and health may involve initiation of the signaling pathways related to AA
metabolism in the luminal bacteria of the small intestine.
Content Type Journal Article
Category Original Article
Pages 1-12
DOI 10.1007/s00726-012-1264-4
Authors
Zhao-Lai Dai, Laboratory of Gastrointestinal Microbiology, Nanjing Agricultural University, Nanjing, 210095 China
Xi-Long Li, Department of Animal Science, Texas A&M University, College Station, TX 77843, USA
Peng-Bin Xi, Department of Animal Science, Texas A&M University, College Station, TX 77843, USA
Jing Zhang, Laboratory of Gastrointestinal Microbiology, Nanjing Agricultural University, Nanjing, 210095 China
Guoyao Wu, Department of Animal Science, Texas A&M University, College Station, TX 77843, USA
Wei-Yun Zhu, Laboratory of Gastrointestinal Microbiology, Nanjing Agricultural University, Nanjing, 210095 China
Diabetes mellitus (DM) is a progressive disorder with severe late complications. Normal wound healing involves a series of
complex and well-orchestrated molecular events dictated by multiple factors. In diabetes, wound healing is grossly impaired
due to defective, and dysregulated cellular and molecular events at all phases of wound healing resulting in chronic wounds
that fail to heal. Carnosine, a dipeptide of alanine and histidine and an endogenous antioxidant is documented to accelerate
healing of wounds and ulcers. However, not much is known about its role in wound healing in diabetes. Therefore, we studied
the effect of carnosine in wound healing in db/db mice, a mice model of Type 2 DM. Six millimeter circular wounds were made
in db/db mice and analyzed for wound healing every other day. Carnosine (100 mg/kg) was injected (I.P.) every day and also
applied locally. Treatment with carnosine enhanced wound healing significantly, and wound tissue analysis showed increased
expression of growth factors and cytokines genes involved in wound healing. In vitro studies with human dermal fibroblasts
and microvascular-endothelial cells showed that carnosine increases cell viability in presence of high glucose. These effects,
in addition to its known role as an antioxidant and a precursor for histamine synthesis, provide evidence for a possible therapeutic
use of carnosine in diabetic wound healing.
Content Type Journal Article
Category Original Article
Pages 1-8
DOI 10.1007/s00726-012-1269-z
Authors
Ishrath Ansurudeen, Department of Molecular Medicine and Surgery, Rolf Luft Centrum, Karolinska Institutet, Stockholm, Solna, Sweden
Vivekananda Gupta Sunkari, Department of Molecular Medicine and Surgery, Rolf Luft Centrum, Karolinska Institutet, Stockholm, Solna, Sweden
Jacob Grünler, Department of Molecular Medicine and Surgery, Rolf Luft Centrum, Karolinska Institutet, Stockholm, Solna, Sweden
Verena Peters, Centre for Pediatric and Adolescent Medicine, Im Neuenheimer Feld 153, 69120 Heidelberg, Germany
Claus Peter Schmitt, Centre for Pediatric and Adolescent Medicine, Im Neuenheimer Feld 153, 69120 Heidelberg, Germany
Sergiu-Bogdan Catrina, Department of Molecular Medicine and Surgery, Rolf Luft Centrum, Karolinska Institutet, Stockholm, Solna, Sweden
Kerstin Brismar, Department of Molecular Medicine and Surgery, Rolf Luft Centrum, Karolinska Institutet, Stockholm, Solna, Sweden
Elisabete Alcantara Forsberg, Department of Molecular Medicine and Surgery, Rolf Luft Centrum, Karolinska Institutet, Stockholm, Solna, Sweden
HSP72 is rapidly expressed in response to a variety of stressors in vitro and in vivo (including hypoxia). This project sought
a hypoxic stimulus to elicit increases in HSP72 and HSP32 in attempts to confer protection to the sub-maximal aerobic exercise-induced
disturbances to redox balance. Eight healthy recreationally active male subjects were exposed to five consecutive days of
once-daily hypoxia (2,980 m, 75 min). Seven days prior to the hypoxic acclimation period, subjects performed 60 min of cycling
on a cycle ergometer (exercise bout 1—EXB1), and this exercise bout was repeated 1 day post-cessation of the hypoxic period
(exercise bout 2—EXB2). Blood samples were taken immediately pre- and post-exercise and 1, 4 and 8 h post-exercise for HSP72
and immediately pre, post and 1 h post-exercise for HSP32, TBARS and glutathione [reduced (GSH), oxidised (GSSG) and total
(TGSH)], with additional blood samples obtained immediately pre-day 1 and post-day 5 of the hypoxic acclimation period for
the same indices. Monocyte-expressed HSP32 and HSP72 were analysed by flow cytometry, with measures of oxidative stress accessed
by commercially available kits. There were significant increases in HSP72 (P < 0.001), HSP32 (P = 0.03), GSSG (t = 9.5, P < 0.001) and TBARS (t = 5.6, P = 0.001) in response to the 5-day hypoxic intervention, whereas no significant changes were observed for GSH (P = 0.22) and TGSH (P = 0.25). Exercise-induced significant increases in HSP72 (P < 0.001) and HSP32 (P = 0.003) post-exercise in EXB1; this response was absent for HSP72 (P ? 0.79) and HSP32 (P ? 0.99) post-EXB2. The hypoxia-mediated increased bio-available HSP32 and HSP72 and favourable alterations in glutathione
redox, prior to exercise commencing in EXB2 compared to EXB1, may acquiesce the disturbances to redox balance encountered
during the second physiologically identical exercise bout.
Content Type Journal Article
Category Original Article
Pages 1-12
DOI 10.1007/s00726-012-1265-3
Authors
Lee Taylor, Muscle Cellular and Molecular Physiology (MCMP) and Applied Sport and Exercise Science (ASEP) Research Groups, Department of Sport and Exercise Sciences, Institute of Sport and Physical Activity Research (ISPAR), University of Bedfordshire, Polhill Campus, Polhill Avenue, Bedford, Bedfordshire MK41 9EA, UK
Angela R. Hillman, Department of Sport, Health and Exercise Science, University of Hull, Hull, UK
Adrian W. Midgley, Department of Sport, Health and Exercise Science, University of Hull, Hull, UK
Daniel J. Peart, Department of Sport, Health and Exercise Science, University of Hull, Hull, UK
Bryna Chrismas, Muscle Cellular and Molecular Physiology (MCMP) and Applied Sport and Exercise Science (ASEP) Research Groups, Department of Sport and Exercise Sciences, Institute of Sport and Physical Activity Research (ISPAR), University of Bedfordshire, Polhill Campus, Polhill Avenue, Bedford, Bedfordshire MK41 9EA, UK
Lars R. McNaughton, Department of Sport, Health and Exercise Science, University of Hull, Hull, UK
Reducing the complexity of plasma proteome through complex multidimensional fractionation protocols is critical for the detection
of low abundance proteins that have the potential to be the most specific disease biomarkers. Therefore, we examined a four
dimension profiling method, which includes low abundance protein enrichment, tryptic digestion and peptide fractionation by
IEF, SCX and RP-LC. The application of peptide pI filtering as an additional criterion for the validation of the identifications
allows to minimize the false discovery rate and to optimize the best settings of the protein identification database search
engine. This sequential approach allows for the identification of low abundance proteins, such as angiogenin (10?9 g/L), pigment epithelium growth factor (10?8 g/L), hepatocyte growth factor activator (10?7 g/L) and thrombospondin-1 (10?6 g/L), having concentrations similar to those of many other growth factors and cytokines involved in disease pathophysiology.
Content Type Journal Article
Category Short Communication
Pages 1-4
DOI 10.1007/s00726-012-1267-1
Authors
Renato Millioni, Department of Medicine, University of Padua, Padua, Italy
Serena Tolin, Department of Medicine, University of Padua, Padua, Italy
Gian Paolo Fadini, Department of Medicine, University of Padua, Padua, Italy
Marco Falda, Department of Biological Chemistry, University of Padua, Padua, Italy
Bas van Breukelen, Biomolecular Mass Spectrometry and Proteomics Group, Bijvoet Centre for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University and Netherlands Proteomics Centre, Padualaan 8, 3584 CH Utrecht, The Netherlands
Paolo Tessari, Department of Medicine, University of Padua, Padua, Italy
Giorgio Arrigoni, Proteomics Centre of Padua University, VIMM and Padua University Hospital, Padua, Italy
The aim of this study was to examine the effect of ?-alanine supplementation on repeated sprint performance during an intermittent
exercise protocol designed to replicate games play. Sixteen elite and twenty non-elite game players performed the Loughborough
Intermittent Shuttle Test (LIST) on two separate occasions. Trials were separated by 4 weeks of supplementation with either
?-alanine (BA) or maltodextrin (MD). There was no deterioration in sprint times from Set 1 to Set 6 of the LIST in either
group prior to supplementation (elite: P = 0.92; non-elite: P = 0.12). Neither BA nor MD supplementation affected sprint times. Blood lactate concentrations were elevated during exercise
in both groups, with no effect of supplementation. ?-Alanine supplementation did not significantly improve sprint performance
during the LIST. Neither group showed a performance decrement prior to supplementation, which might have masked any benefit
from increased muscle buffering capacity due to ?-alanine supplementation.
Content Type Journal Article
Category Original Article
Pages 1-9
DOI 10.1007/s00726-012-1268-0
Authors
Bryan Saunders, Sport, Health and Performance Enhancement (SHAPE) Research Group, School of Science and Technology, Nottingham Trent University, Clifton Lane, Nottingham, NG11 8NS UK
Craig Sale, Sport, Health and Performance Enhancement (SHAPE) Research Group, School of Science and Technology, Nottingham Trent University, Clifton Lane, Nottingham, NG11 8NS UK
Roger C. Harris, Junipa Ltd, Newmarket, Suffolk, CB8 8HD UK
Caroline Sunderland, Sport, Health and Performance Enhancement (SHAPE) Research Group, School of Science and Technology, Nottingham Trent University, Clifton Lane, Nottingham, NG11 8NS UK
Aliphatic polyamines, being a versatile class of organic compounds, are widely used in many fields of medicine and organic
chemistry. However, the general approach to the synthesis of chiral aliphatic polyamines has been still undeveloped. Here,
we describe a new method for the synthesis of chiral trifunctional amino compounds, namely hydroxydiamines and triamines.
The initial compounds, namely substituted hydroxy- or aminopyrazolidines and pyrazolines, are readily available using convenient
stereoselective methods developed earlier by us. The proposed method allows synthesizing of chiral diaminoalcohols and triamines,
which are the analogs of a well-known anti-TB drug, namely ethambutol, and cannot be obtained alternatively. The key step
of the synthesis is N–N bond cleavage in substituted hydroxy- or aminopyrazolidines and pyrazolines with borane-tetrahydrofuran
complex; other known methods for N–N bond cleavage turned out to be ineffective. The main advantage of the proposed method
is the retention of a certain configuration of stereocenters in the course of the reaction. Six new chiral diasteomerically
pure substituted hydroxydiamines and triamines and the enantiomerically pure triamine with four chiral centers were synthesized
and characterized using NMR, IR and mass spectroscopy, as well as elemental analysis.
Content Type Journal Article
Category Original Article
Pages 1-7
DOI 10.1007/s00726-011-1187-5
Authors
Ludmila A. Sviridova, Department of Chemistry, M. V. Lomonosov Moscow State University, 119899 Moscow, Russian Federation
Galina A. Golubeva, Department of Chemistry, M. V. Lomonosov Moscow State University, 119899 Moscow, Russian Federation
Alexander N. Tavtorkin, Department of Chemistry, M. V. Lomonosov Moscow State University, 119899 Moscow, Russian Federation
Konstantin A. Kochetkov, A. N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, 119991 Moscow, Russian Federation
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