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Pesquisa : D12.125.067.500.150 [Categoria DeCS]
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[PMID]:28841667
[Au] Autor:Melville GW; Siegler JC; Marshall PWM
[Ad] Endereço:School of Science and Health, Western Sydney University, Sydney, Australia.
[Ti] Título:The effects of d-aspartic acid supplementation in resistance-trained men over a three month training period: A randomised controlled trial.
[So] Source:PLoS One;12(8):e0182630, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:CONTEXT: Research on d-aspartic acid (DAA) has demonstrated increases in total testosterone levels in untrained men, however research in resistance-trained men demonstrated no changes, and reductions in testosterone levels. The long-term consequences of DAA in a resistance trained population are currently unknown. OBJECTIVE: To evaluate the effectiveness of DAA to alter basal testosterone levels over 3 months of resistance training in resistance-trained men. DESIGN: Randomised, double-blind, placebo controlled trial in healthy resistance-trained men, aged 18-36, had been performing regular resistance training exercise for at least 3 d.w-1 for the previous 2 years. Randomised participants were 22 men (d-aspartic acid n = 11; placebo n = 11) (age, 23.8±4.9 y, training age, 3.2±1.5 y). INTERVENTION: D-aspartic acid (6 g.d-1, DAA) versus equal-weight, visually-matched placebo (PLA). All participants performed 12 weeks of supervised, periodised resistance training (4 d.w-1), with a program focusing on all muscle groups. MEASURES: Basal hormones, total testosterone (TT), free testosterone (FT), estradiol (E2), sex-hormone-binding globulin (SHBG) and albumin (ALB); isometric strength; calf muscle cross-sectional area (CSA); calf muscle thickness; quadriceps muscle CSA; quadriceps muscle thickness; evoked V-wave and H-reflexes, were assessed at weeks zero (T1), after six weeks (T2) and after 12 weeks (T3). RESULTS: No change in basal TT or FT were observed after the intervention. DAA supplementation (n = 10) led to a 16%, 95% CI [-27%, -5%] reduction in E2 from T1-T3 (p<0.01). The placebo group (n = 9) demonstrated improvements in spinal responsiveness (gastrocnemius) at the level of the alpha motoneuron. Both groups exhibited increases in isometric strength of the plantar flexors by 17%, 95% CI [7%, 28%] (p<0.05) as well as similar increases in hypertrophy in the quadriceps and calf muscles. CONCLUSIONS: The results of this paper indicate that DAA supplementation is ineffective at changing testosterone levels, or positively affecting training outcomes. Reductions in estradiol and the blunting of peripheral excitability appear unrelated to improvements from resistance training. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12617000041358.
[Mh] Termos MeSH primário: Ácido D-Aspártico/administração & dosagem
Suplementos Nutricionais
Levantamento de Peso
[Mh] Termos MeSH secundário: Adulto
Método Duplo-Cego
Eletromiografia
Seres Humanos
Masculino
Placebos
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Placebos); 4SR0Q8YD1X (D-Aspartic Acid)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171023
[Lr] Data última revisão:
171023
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170826
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0182630


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[PMID]:28264757
[Au] Autor:Barbato V; Talevi R; Braun S; Merolla A; Sudhakaran S; Longobardi S; Gualtieri R
[Ad] Endereço:Dipartimento di Biologia,Università di Napoli 'Federico II',Complesso Universitario di Monte S Angelo,Via Cinthia,80126 Napoli,Italy.
[Ti] Título:Supplementation of sperm media with zinc, D-aspartate and co-enzyme Q10 protects bull sperm against exogenous oxidative stress and improves their ability to support embryo development.
[So] Source:Zygote;25(2):168-175, 2017 Apr.
[Is] ISSN:1469-8730
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:High levels of reactive oxygen species in the semen of infertile patients or spontaneously generated during in vitro sperm handling may impair sperm quality, fertilization and embryo developmental competence. We recently reported that zinc, d-aspartate and co-enzyme Q10, contained in the dietary supplement Genadis® (Merck Serono), have protective effects on human and bull sperm motility, lipid peroxidation and DNA fragmentation in vitro; furthermore, in bovine, treated spermatozoa had an improved ability to support embryo development. However, only a few studies have investigated the protective role of antioxidants during in vitro sperm handling in the presence of an exogenous oxidative stress. Herein, to simulate such conditions in an animal model, we induced exogenous oxidative stress on spermatozoa through the xanthine-xanthine oxidase system and investigated its effects on sperm function and subsequent embryo developmental competence in the presence of zinc, d-Asp and CoQ10 protection. The main results showed that exogenous oxidative stress decreased sperm motility, increased sperm DNA fragmentation, and reduced fertilization and blastocyst rates and quality. Pre-treatment with zinc, d-aspartate and co-enzyme Q10 before exogenous oxidative stress was able to prevent these effects. Supplementation of sperm culture media with zinc, d-aspartate and co-enzyme Q10 could protect sperm from oxidative stress damage during in vitro handling in assisted reproductive technologies.
[Mh] Termos MeSH primário: Ácido D-Aspártico/farmacologia
Desenvolvimento Embrionário/efeitos dos fármacos
Estresse Oxidativo/efeitos dos fármacos
Espermatozoides/fisiologia
Ubiquinona/análogos & derivados
Zinco/farmacologia
[Mh] Termos MeSH secundário: Animais
Bovinos
Dano ao DNA/efeitos dos fármacos
Peroxidação de Lipídeos/efeitos dos fármacos
Masculino
Espécies Reativas de Oxigênio/metabolismo
Motilidade Espermática/efeitos dos fármacos
Espermatozoides/efeitos dos fármacos
Oligoelementos/farmacologia
Ubiquinona/farmacologia
Vitaminas/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Reactive Oxygen Species); 0 (Trace Elements); 0 (Vitamins); 1339-63-5 (Ubiquinone); 4SR0Q8YD1X (D-Aspartic Acid); EJ27X76M46 (coenzyme Q10); J41CSQ7QDS (Zinc)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171031
[Lr] Data última revisão:
171031
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170308
[St] Status:MEDLINE
[do] DOI:10.1017/S0967199416000459


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[PMID]:28237346
[Au] Autor:Ansari M; Zhandi M; Kohram H; Zaghari M; Sadeghi M; Sharafi M
[Ad] Endereço:Department of Animal Science, College of Agriculture and Natural Resources, University of Tehran, Karaj, 31587-77871, Iran.
[Ti] Título:Improvement of post-thawed sperm quality and fertility of Arian rooster by oral administration of d-aspartic acid.
[So] Source:Theriogenology;92:69-74, 2017 Apr 01.
[Is] ISSN:1879-3231
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:This study was conducted to investigate the effect of d-Aspartic acid (D-Asp) on post-thawed sperm quality, fertility and hatchability outcomes in male broiler breeders. Twenty 55-week-old roosters were selected and equally split into four groups (n = 5 rooster/group). Different daily D-Asp doses including 0 (D-0), 100 (D-100), 200 (D-200) or 300 (D-300) mg/kg BW were capsulated and individually administered for 12 weeks to roosters in each group. Semen samples were weekly collected from 7th to 12th week of experiment. Sperm quality from 7th to 11th week was evaluated in both fresh (total and forward motility and plasma membrane functionality) and post-thawed (total and forward motility, plasma membrane functionality, apoptosis status and mitochondrial activity) conditions. Also, collected semen samples on the 12th week were frozen and artificially inseminated to evaluate fertility and hatchability. The results from fresh condition showed that total and forward motility and plasma membrane functionality were significantly higher in D-200 compared to other groups. Also, interaction effect of time and treatment was not significant for all assessed parameters in fresh condition. In post-thawed condition, D-200 showed significantly higher total and forward motility, fertility and hatchability compared to other groups. The higher value for plasma membrane functionality and mitochondrial activity was observed in D-200 compared to D-0 and D300 groups. However, the percentage of live, early apoptotic and dead spermatozoa were not significantly affected by applied treatment in the current study. No significant difference for time and treat interaction effect was observed for all assessed parameters except forward motility. In conclusion, it seems that D-Asp administration could improve fresh and post-thawed sperm quality and post-thawed sperm fertility in male broiler breeders.
[Mh] Termos MeSH primário: Galinhas/fisiologia
Ácido D-Aspártico/farmacologia
Análise do Sêmen/veterinária
Preservação do Sêmen/veterinária
Espermatozoides/fisiologia
[Mh] Termos MeSH secundário: Animais
Criopreservação
Ácido D-Aspártico/administração & dosagem
Fertilidade
Congelamento
Masculino
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
4SR0Q8YD1X (D-Aspartic Acid)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170811
[Lr] Data última revisão:
170811
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170227
[St] Status:MEDLINE


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[PMID]:27422792
[Au] Autor:Giacone F; Condorelli RA; Mongioì LM; Bullara V; La Vignera S; Calogero AE
[Ad] Endereço:Department of Clinical and Experimental Medicine, University of Catania, Policlinico "G. Rodolico", via S. Sofia 78, Catania, 95123, Italy.
[Ti] Título:In vitro effects of zinc, D-aspartic acid, and coenzyme-Q10 on sperm function.
[So] Source:Endocrine;56(2):408-415, 2017 May.
[Is] ISSN:1559-0100
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Reactive oxygen species favor reproductive processes at low concentrations, but damage spermatozoa and decrease their fertilizing capacity at high concentrations. During infection and/or inflammation of the accessory sex glands reactive oxygen species overproduction may occur which, in turn, may negatively impact on sperm motility, sperm DNA fragmentation, and lipid peroxidation. A number of nutraceutical formulations containing antioxidant molecules have been developed to counteract the deleterious effects of the oxidative stress. A recent formulation containing zinc, D-aspartic acid, and coenzyme-Q10 is present in the pharmaceutical market. Based on these premises, the aim of the present study was to evaluate the effects of this combination on spermatozoa in vitro. The study was conducted on 24 men (32.2 ± 5.5 years): 12 normozoospermic men and 12 asthenozoospermic patients. Spermatozoa from each sample were divided into two control aliquots (aliquot A and B) and an aliquot incubated with zinc, D-aspartic acid, and coenzyme-Q10 (aliquot C). After 3 h of incubation, the following parameters were evaluated: progressive motility, number of spermatozoa with progressive motility recovered after swim-up, lipid peroxidation, and DNA fragmentation. Incubation with zinc, D-aspartic acid, and coenzyme-Q10 maintained sperm motility in normozoospermic men (37.7 ± 1.2 % vs. 35.8 ± 2.3 % at time zero) and improved it significantly in asthenozoospermic patients (26.5 ± 1.9 % vs. 18.8 ± 2.0 % at time zero) (p < 0.01). This resulted in a significantly higher (p < 0.01) number of spermatozoa with progressive motility recovered after swim-up in both normozospermic men (4.1 ± 0.9 vs. 3.3 ± 1.0 millions) and asthenozooseprmic patients (3.2 ± 0.8 vs. 1.6 ± 0.5 millions). Finally, a statistically significant lower sperm lipid peroxidation was found after incubation with zinc, D-aspartic acid, and coenzyme-Q10 (p < 0.05) in both normozospermic men (1.0 ± 0.4 % vs. 2.4 ± 0.9 %) and asthenozooseprmic patients (0.2 ± 0.1 % vs. 0.6 ± 0.2 %). No statistically significant effect was observed on sperm DNA fragmentation. This nutraceutical formulation may be indicated in vitro during the separation of the spermatozoa in the assisted reproduction techniques, during which the spermatozoa undergo an increased oxidative stress.
[Mh] Termos MeSH primário: Ácido D-Aspártico/farmacologia
Estresse Oxidativo/efeitos dos fármacos
Motilidade Espermática/efeitos dos fármacos
Espermatozoides/efeitos dos fármacos
Ubiquinona/análogos & derivados
Zinco/farmacologia
[Mh] Termos MeSH secundário: Adulto
Astenozoospermia/fisiopatologia
Fragmentação do DNA/efeitos dos fármacos
Seres Humanos
Peroxidação de Lipídeos/efeitos dos fármacos
Masculino
Espermatozoides/fisiologia
Ubiquinona/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
1339-63-5 (Ubiquinone); 4SR0Q8YD1X (D-Aspartic Acid); EJ27X76M46 (coenzyme Q10); J41CSQ7QDS (Zinc)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171107
[Lr] Data última revisão:
171107
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160717
[St] Status:MEDLINE
[do] DOI:10.1007/s12020-016-1013-7


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[PMID]:27435686
[Au] Autor:Mizuno H; Miyazaki Y; Ito K; Todoroki K; Min JZ; Toyo'oka T
[Ad] Endereço:Laboratory of Analytical and Bioanalytical Chemistry, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka, 422-8526, Japan.
[Ti] Título:A rapid and sensitive detection of D-Aspartic acid in Crystallin by chiral derivatized liquid chromatography mass spectrometry.
[So] Source:J Chromatogr A;1467:318-325, 2016 Oct 07.
[Is] ISSN:1873-3778
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:A method for the determination of D-Aspartic acid (D-Asp) and its D/L ratio in peptides and proteins has been developed. This method was carried out with good separation of the D/L chiral peptide pairs by combination of a chiral derivatization and an ADME column separation. Furthermore, a cationic derivatization reagent, DBD-Py-NCS, increased the sensitivity of the ESI-MS/MS detection. To confirm the comprehensive peptide analysis, synthesized α-Crystallin tryptic peptides, which included D-Asp residues, were analyzed. The 5 pairs of D/L-Asp that included peptide diastereomers were well separated. Their peak resolutions were more than 1.5 and the results were reproducible (RSD<0.05, n=5). As an application of this method, we analyzed the α-Crystallin standard and UV irradiated α-Crystallin. After trypsin digestion and DBD-Py-NCS derivatization, the tryptic peptide derivatives were applied to LC-MS/MS. Based on the results of peptide sequence identification, almost all the tryptic peptides of the αA- and αB-Crystallin homologous subunits of α-Crystallin were detected as DBD-Py NCS derivatives. However, there was no D-Asp residue in the standard proteins. In the case of the UV irradiated α-Crystallin, Asp and Asp in the αA-Crystallin and Asp in αB-Crystallin were racemized to D-Asp. These results show that this proposed chiral peptide LC-MS/MS method using chiral derivatization provides a rapid and sensitive analysis for post translational Asp racemization sites in aging proteins.
[Mh] Termos MeSH primário: Cristalinas/química
Ácido D-Aspártico/análise
[Mh] Termos MeSH secundário: Cromatografia Líquida
Ácido D-Aspártico/química
Indicadores e Reagentes
Isotiocianatos/química
Oxidiazóis/química
Peptídeos/química
Estereoisomerismo
Espectrometria de Massas em Tandem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (4-(3-isothiocyanatopyrrolidin-1-yl)-7-(N,N-dimethylaminosulfonyl)-2,1,3-benzoxadiazole); 0 (Crystallins); 0 (Indicators and Reagents); 0 (Isothiocyanates); 0 (Oxadiazoles); 0 (Peptides); 4SR0Q8YD1X (D-Aspartic Acid)
[Em] Mês de entrada:1612
[Cu] Atualização por classe:171008
[Lr] Data última revisão:
171008
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160721
[St] Status:MEDLINE


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[PMID]:27435607
[Au] Autor:Szöko É; Vincze I; Tábi T
[Ad] Endereço:Department of Pharmacodynamics, Semmelweis University, Nagyvárad tér 4. Budapest, H-1089, Hungary. Electronic address: szoko.eva@pharma.semmelweis-univ.hu.
[Ti] Título:Chiral separations for d-amino acid analysis in biological samples.
[So] Source:J Pharm Biomed Anal;130:100-109, 2016 Oct 25.
[Is] ISSN:1873-264X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:It is widely accepted that some of the free d-amino acids play important biological role. d-Aspartate and d-serine formed in the central nervous system of higher vertebrates have neurotransmitter/neuromodulator function. Together with d-alanine they are distributed in various tissues and biological fluids. Studying their physiological and pathological significance requires their sensitive and accurate determination in biological samples. The various separation and detection methods used for their analysis are overviewed in the present paper. Our focus is mainly the quantitative performance and the analysis of real biospecimens.
[Mh] Termos MeSH primário: Aminoácidos/análise
Aminoácidos/química
Líquidos Corporais/química
[Mh] Termos MeSH secundário: Alanina/análise
Alanina/química
Alanina/metabolismo
Aminoácidos/metabolismo
Animais
Líquidos Corporais/metabolismo
Cromatografia Líquida de Alta Pressão/métodos
Ácido D-Aspártico/análise
Ácido D-Aspártico/química
Ácido D-Aspártico/metabolismo
Eletroforese Capilar/métodos
Seres Humanos
Serina/análise
Serina/química
Serina/metabolismo
Estereoisomerismo
Distribuição Tecidual/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Amino Acids); 452VLY9402 (Serine); 4SR0Q8YD1X (D-Aspartic Acid); OF5P57N2ZX (Alanine)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170904
[Lr] Data última revisão:
170904
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160721
[St] Status:MEDLINE


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[PMID]:27428949
[Au] Autor:Di Fiore MM; Santillo A; Falvo S; Longobardi S; Chieffi Baccari G
[Ad] Endereço:Dipartimento di Scienze e Tecnologie Ambientali, Biologiche e Farmaceutiche, Seconda Università di Napoli, Via Vivaldi 43, 81100 Caserta, Italy. MariaM.DiFiore@unina2.it.
[Ti] Título:Molecular Mechanisms Elicited by d-Aspartate in Leydig Cells and Spermatogonia.
[So] Source:Int J Mol Sci;17(7), 2016 Jul 14.
[Is] ISSN:1422-0067
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:A bulk of evidence suggests that d-aspartate (d-Asp) regulates steroidogenesis and spermatogenesis in vertebrate testes. This review article focuses on intracellular signaling mechanisms elicited by d-Asp possibly via binding to the N-methyl-d-aspartate receptor (NMDAR) in both Leydig cells, and spermatogonia. In Leydig cells, the amino acid upregulates androgen production by eliciting the adenylate cyclase-cAMP and/or mitogen-activated protein kinase (MAPK) pathways. d-Asp treatment enhances gene and protein expression of enzymes involved in the steroidogenic cascade. d-Asp also directly affects spermatogonial mitotic activity. In spermatogonial GC-1 cells, d-Asp induces phosphorylation of MAPK and AKT serine-threonine kinase proteins, and stimulates expression of proliferating cell nuclear antigen (PCNA) and aurora kinase B (AURKB). Further stimulation of spermatogonial GC-1 cell proliferation might come from estradiol/estrogen receptor ß (ESR2) interaction. d-Asp modulates androgen and estrogen levels as well as the expression of their receptors in the rat epididymis by acting on mRNA levels of Srd5a1 and Cyp19a1 enzymes, hence suggesting involvement in spermatozoa maturation.
[Mh] Termos MeSH primário: Ácido D-Aspártico/farmacologia
Células Intersticiais do Testículo/efeitos dos fármacos
Espermatogônias/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Seres Humanos
Masculino
Ratos
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
4SR0Q8YD1X (D-Aspartic Acid)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:170321
[Lr] Data última revisão:
170321
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160719
[St] Status:MEDLINE


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[PMID]:27387750
[Au] Autor:Ito T; Hayashida M; Kobayashi S; Muto N; Hayashi A; Yoshimura T; Mori H
[Ad] Endereço:Department of Applied Molecular Biosciences, Graduate School of Bioagricultural Sciences, Nagoya University, Furo-Cho, Chikusa-Ku, Nagoya, Aichi 464-8601, Japan.
[Ti] Título:Serine racemase is involved in d-aspartate biosynthesis.
[So] Source:J Biochem;160(6):345-353, 2016 Dec.
[Is] ISSN:1756-2651
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:d-Aspartate is found in the nervous and reproductive system and participates in various physiological roles. While several lines of evidence suggest that this amino acid has an endogenous origin, the enzyme responsible for mammalian d-Asp biosynthesis has not yet been identified. We show that mammalian serine racemase (SRR), the primary enzyme responsible for brain d-Ser production, catalyses Asp racemization via a two-base mechanism. We observed that overexpression of SRR in rat pheochromocytoma PC12 cells resulted in an increase in intracellular d-Asp compared with control cells, demonstrating that SRR functions as an Asp racemase in the cells. To investigate the impact of endogenous SRR on endogenous d-Asp levels in the cells, we generated SRR-knockout (SRR-KO) PC12 cells. The SRR-KO cells exhibited decreased intracellular d-Ser levels, but production levels of d-Asp were unaffected. In contrast, SRR-KO mice showed significantly decreased d-Asp levels in their frontal cortices and hippocampi, where SRR is normally highly expressed, while d-Asp levels in the cerebellum and testes remained unchanged. Our results indicate that SRR indeed acts as a d-Asp biosynthetic enzyme in some organs and/or tissues, and also provide evidences that there should be some additional enzyme for d-Asp synthesis in mammals.
[Mh] Termos MeSH primário: Ácido D-Aspártico/biossíntese
Lobo Frontal/metabolismo
Hipocampo/metabolismo
Racemases e Epimerases/metabolismo
Testículo/metabolismo
[Mh] Termos MeSH secundário: Animais
Ácido D-Aspártico/genética
Técnicas de Silenciamento de Genes
Masculino
Camundongos
Camundongos Knockout
Células PC12
Racemases e Epimerases/genética
Ratos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
4SR0Q8YD1X (D-Aspartic Acid); EC 5.1.- (Racemases and Epimerases); EC 5.1.1.16 (serine racemase)
[Em] Mês de entrada:1701
[Cu] Atualização por classe:170130
[Lr] Data última revisão:
170130
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160709
[St] Status:MEDLINE


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[PMID]:26961959
[Au] Autor:Punzo D; Errico F; Cristino L; Sacchi S; Keller S; Belardo C; Luongo L; Nuzzo T; Imperatore R; Florio E; De Novellis V; Affinito O; Migliarini S; Maddaloni G; Sisalli MJ; Pasqualetti M; Pollegioni L; Maione S; Chiariotti L; Usiello A
[Ad] Endereço:Istituto di Endocrinologia ed Oncologia Sperimentale, Consiglio Nazionale delle Ricerche (CNR), 80131 Naples, Italy, Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, Second University of Naples, 81100 Caserta, Italy.
[Ti] Título:Age-Related Changes in D-Aspartate Oxidase Promoter Methylation Control Extracellular D-Aspartate Levels and Prevent Precocious Cell Death during Brain Aging.
[So] Source:J Neurosci;36(10):3064-78, 2016 Mar 09.
[Is] ISSN:1529-2401
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The endogenous NMDA receptor (NMDAR) agonist D-aspartate occurs transiently in the mammalian brain because it is abundant during embryonic and perinatal phases before drastically decreasing during adulthood. It is well established that postnatal reduction of cerebral D-aspartate levels is due to the concomitant onset of D-aspartate oxidase (DDO) activity, a flavoenzyme that selectively degrades bicarboxylic D-amino acids. In the present work, we show that d-aspartate content in the mouse brain drastically decreases after birth, whereas Ddo mRNA levels concomitantly increase. Interestingly, postnatal Ddo gene expression is paralleled by progressive demethylation within its putative promoter region. Consistent with an epigenetic control on Ddo expression, treatment with the DNA-demethylating agent, azacitidine, causes increased mRNA levels in embryonic cortical neurons. To indirectly evaluate the effect of a putative persistent Ddo gene hypermethylation in the brain, we used Ddo knock-out mice (Ddo(-/-)), which show constitutively suppressed Ddo expression. In these mice, we found for the first time substantially increased extracellular content of d-aspartate in the brain. In line with detrimental effects produced by NMDAR overstimulation, persistent elevation of D-aspartate levels in Ddo(-/-) brains is associated with appearance of dystrophic microglia, precocious caspase-3 activation, and cell death in cortical pyramidal neurons and dopaminergic neurons of the substantia nigra pars compacta. This evidence, along with the early accumulation of lipufuscin granules in Ddo(-/-) brains, highlights an unexpected importance of Ddo demethylation in preventing neurodegenerative processes produced by nonphysiological extracellular levels of free D-aspartate.
[Mh] Termos MeSH primário: Envelhecimento
Encéfalo/metabolismo
D-Aspartato Oxidase/metabolismo
Ácido D-Aspártico/metabolismo
Neurônios/fisiologia
Regiões Promotoras Genéticas/genética
[Mh] Termos MeSH secundário: Fatores Etários
Animais
Animais Recém-Nascidos
Azacitidina/análogos & derivados
Azacitidina/farmacologia
Encéfalo/citologia
Morte Celular/genética
D-Aspartato Oxidase/genética
Embrião de Mamíferos
Inibidores Enzimáticos/farmacologia
Masculino
Metilação
Camundongos
Camundongos Endogâmicos C57BL
Camundongos Transgênicos
Neurônios/efeitos dos fármacos
RNA Mensageiro/metabolismo
Receptores de N-Metil-D-Aspartato/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Enzyme Inhibitors); 0 (RNA, Messenger); 0 (Receptors, N-Methyl-D-Aspartate); 4SR0Q8YD1X (D-Aspartic Acid); 776B62CQ27 (decitabine); EC 1.4.3.1 (D-Aspartate Oxidase); M801H13NRU (Azacitidine)
[Em] Mês de entrada:1607
[Cu] Atualização por classe:160310
[Lr] Data última revisão:
160310
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160311
[St] Status:MEDLINE
[do] DOI:10.1523/JNEUROSCI.3881-15.2016


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[PMID]:26876027
[Au] Autor:Aki K; Okamura E
[Ad] Endereço:Faculty of Pharmaceutical Sciences, Himeji Dokkyo University, 7-2-1 Kamiohno, Himeji 670-8524, Japan.
[Ti] Título:D-ß-aspartyl residue exhibiting uncommon high resistance to spontaneous peptide bond cleavage.
[So] Source:Sci Rep;6:21594, 2016 Feb 15.
[Is] ISSN:2045-2322
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Although L-amino acids were selected as main constituents of peptides and proteins during chemical evolution, D-aspartyl (Asp) residue is found in a variety of living tissues. In particular, D-ß-Asp is thought to be stable than any other Asp isomers, and this could be a reason for gradual accumulation in abnormal proteins and peptides to modify their structures and functions. It is predicted that D-ß-Asp shows high resistance to biomolecular reactions. For instance, less reactivity of D-ß-Asp is expected to bond cleavage, although such information has not been provided yet. In this work, the spontaneous peptide bond cleavage was compared between Asp isomers, by applying real-time solution-state NMR to eye lens αΑ-crystallin 51-60 fragment, S(51)LFRTVLD(58)SG(60) and αΒ-crystallin 61-67 analog, F(61)D(62)TGLSG(67) consisting of L-α- and D-ß-Asp 58 and 62, respectively. Kinetic analysis showed how tough the uncommon D-ß-Asp residue was against the peptide bond cleavage as compared to natural L-α-Asp. Differences in pKa and conformation between L-α- and D-ß-Asp side chains were plausible factors to determine reactivity of Asp isomers. The present study, for the first time, provides a rationale to explain less reactivity of D-ß-Asp to allow abnormal accumulation.
[Mh] Termos MeSH primário: Ácido D-Aspártico/metabolismo
Ácido Isoaspártico/metabolismo
Proteólise
[Mh] Termos MeSH secundário: Ácido D-Aspártico/química
Ácido D-Aspártico/farmacocinética
Seres Humanos
Ácido Isoaspártico/química
Ácido Isoaspártico/farmacocinética
Isomerismo
Cristalino/química
Ressonância Magnética Nuclear Biomolecular
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Isoaspartic Acid); 4SR0Q8YD1X (D-Aspartic Acid)
[Em] Mês de entrada:1701
[Cu] Atualização por classe:170116
[Lr] Data última revisão:
170116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160216
[St] Status:MEDLINE
[do] DOI:10.1038/srep21594



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