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[PMID]:28942274
[Au] Autor:Andersson M; Karlsson O; Brandt I
[Ad] Endereço:Department of Environmental Toxicology, Uppsala University, SE-752 36 Uppsala, Sweden.
[Ti] Título:The environmental neurotoxin ß-N-methylamino-l-alanine (l-BMAA) is deposited into birds' eggs.
[So] Source:Ecotoxicol Environ Saf;147:720-724, 2018 Jan.
[Is] ISSN:1090-2414
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:The neurotoxic amino acid ß-N-methylamino-L-alanine (BMAA) has been implicated in the etiology of neurodegenerative disorders. BMAA is also a known developmental neurotoxin and research indicates that the sources of human and wildlife exposure may be more diverse than previously anticipated. The aim of the present study was therefore to examine whether BMAA can be transferred into birds' eggs. Egg laying quail were dosed with C-labeled BMAA. The distribution of radioactivity in the birds and their laid eggs was then examined at different time points by autoradiography and phosphoimaging analysis. To evaluate the metabolic stability of the BMAA molecule, the distribution of C-methyl- and C-carboxyl-labeled BMAA were compared. The results revealed a pronounced incorporation of radioactivity in the eggs, predominantly in the yolk but also in the albumen. Imaging analysis showed that the concentrations of radioactivity in the liver decreased about seven times between the 24h and the 72h time points, while the concentrations in egg yolk remained largely unchanged. At 72h the egg yolk contained about five times the concentration of radioactivity in the liver. Both BMAA preparations gave rise to similar distribution pattern in the bird tissues and in the eggs, indicating metabolic stability of the labeled groups. The demonstrated deposition into eggs warrants studies of BMAAs effects on bird development. Moreover, birds' eggs may be a source of human BMAA exposure, provided that the laying birds are exposed to BMAA via their diet.
[Mh] Termos MeSH primário: Diamino Aminoácidos/toxicidade
Aves/metabolismo
Monitoramento Ambiental/métodos
Poluentes Ambientais/toxicidade
Neurotoxinas/toxicidade
Óvulo/metabolismo
[Mh] Termos MeSH secundário: Diamino Aminoácidos/metabolismo
Animais
Autorradiografia
Poluentes Ambientais/metabolismo
Seres Humanos
Neurotoxinas/metabolismo
Distribuição Tecidual
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Amino Acids, Diamino); 0 (Environmental Pollutants); 0 (Neurotoxins); 108SA6URTV (beta-N-methylamino-L-alanine)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170925
[St] Status:MEDLINE


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[PMID]:28598725
[Au] Autor:Chernoff N; Hill DJ; Diggs DL; Faison BD; Francis BM; Lang JR; Larue MM; Le TT; Loftin KA; Lugo JN; Schmid JE; Winnik WM
[Ad] Endereço:a U.S. Environmental Protection Agency, Office of Research and Development , National Health and Environmental Effects Research Laboratory , Research Triangle Park , NC , USA.
[Ti] Título:A critical review of the postulated role of the non-essential amino acid, ß-N-methylamino-L-alanine, in neurodegenerative disease in humans.
[So] Source:J Toxicol Environ Health B Crit Rev;20(4):1-47, 2017.
[Is] ISSN:1521-6950
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The compound BMAA (ß-N-methylamino-L-alanine) has been postulated to play a significant role in four serious neurological human diseases: Amyotrophic Lateral Sclerosis/Parkinsonism Dementia Complex (ALS/PDC) found on Guam, and ALS, Parkinsonism, and dementia that occur globally. ALS/PDC with symptoms of all three diseases first came to the attention of the scientific community during and after World War II. It was initially associated with cycad flour used for food because BMAA is a product of symbiotic cycad root-dwelling cyanobacteria. Human consumption of flying foxes that fed on cycad seeds was later suggested as a source of BMAA on Guam and a cause of ALS/PDC. Subsequently, the hypothesis was expanded to include a causative role for BMAA in other neurodegenerative diseases including Alzheimer's disease (AD) through exposures attributed to proximity to freshwaters and/or consumption of seafood due to its purported production by most species of cyanobacteria. The hypothesis that BMAA is the critical factor in the genesis of these neurodegenerative diseases received considerable attention in the medical, scientific, and public arenas. This review examines the history of ALS/PDC and the BMAA-human disease hypotheses; similarities and differences between ALS/PDC and the other diseases with similar symptomologies; the relationship of ALS/PDC to other similar diseases, studies of BMAA-mediated effects in lab animals, inconsistencies and data gaps in the hypothesis; and other compounds and agents that were suggested as the cause of ALS/PDC on Guam. The review concludes that the hypothesis of a causal BMAA neurodegenerative disease relationship is not supported by existing data.
[Mh] Termos MeSH primário: Diamino Aminoácidos/toxicidade
Cianobactérias/metabolismo
Doenças Neurodegenerativas/etiologia
[Mh] Termos MeSH secundário: Doença de Alzheimer/etiologia
Doença de Alzheimer/fisiopatologia
Esclerose Amiotrófica Lateral/etiologia
Esclerose Amiotrófica Lateral/fisiopatologia
Animais
Cycas/toxicidade
Farinha/toxicidade
Seres Humanos
Doenças Neurodegenerativas/fisiopatologia
Neurotoxinas/toxicidade
Transtornos Parkinsonianos/etiologia
Transtornos Parkinsonianos/fisiopatologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Amino Acids, Diamino); 0 (Neurotoxins); 108SA6URTV (beta-N-methylamino-L-alanine)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170629
[Lr] Data última revisão:
170629
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170610
[St] Status:MEDLINE
[do] DOI:10.1080/10937404.2017.1297592


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[PMID]:28316096
[Au] Autor:Cieslak J; Miyanaga A; Takaku R; Takaishi M; Amagai K; Kudo F; Eguchi T
[Ad] Endereço:Department of Chemistry and Materials Science, Tokyo Institute of Technology, O-okayama, Meguro-ku, Tokyo, 152-8551, Japan.
[Ti] Título:Biochemical characterization and structural insight into aliphatic ß-amino acid adenylation enzymes IdnL1 and CmiS6.
[So] Source:Proteins;85(7):1238-1247, 2017 Jul.
[Is] ISSN:1097-0134
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Macrolactam antibiotics such as incednine and cremimycin possess an aliphatic ß-amino acid as a starter unit of their polyketide chain. In the biosynthesis of incednine and cremimycin, unique stand-alone adenylation enzymes IdnL1 and CmiS6 select and activate the proper aliphatic ß-amino acid as a starter unit. In this study, we describe the enzymatic characterization and the structural basis of substrate specificity of IdnL1 and CmiS6. Functional analysis revealed that IdnL1 and CmiS6 recognize 3-aminobutanoic acid and 3-aminononanoic acid, respectively. We solved the X-ray crystal structures of IdnL1 and CmiS6 to understand the recognition mechanism of these aliphatic ß-amino acids. These structures revealed that IdnL1 and CmiS6 share a common recognition motif that interacts with the ß-amino group of the substrates. However, the hydrophobic side-chains of the substrates are accommodated differently in the two enzymes. IdnL1 has a bulky Leu220 located close to the terminal methyl group of 3-aminobutanoate of the trapped acyl-adenylate intermediate to construct a shallow substrate-binding pocket. In contrast, CmiS6 possesses Gly220 at the corresponding position to accommodate 3-aminononanoic acid. This structural observation was supported by a mutational study. Thus, the size of amino acid residue at the 220 position is critical for the selection of an aliphatic ß-amino acid substrate in these adenylation enzymes. Proteins 2017; 85:1238-1247. © 2017 Wiley Periodicals, Inc.
[Mh] Termos MeSH primário: Diamino Aminoácidos/química
Aminobutiratos/química
Proteínas de Bactérias/química
Nucleotidiltransferases/química
Streptomyces/química
[Mh] Termos MeSH secundário: Motivos de Aminoácidos
Diamino Aminoácidos/metabolismo
Aminobutiratos/metabolismo
Antibacterianos/biossíntese
Proteínas de Bactérias/genética
Proteínas de Bactérias/metabolismo
Sítios de Ligação
Clonagem Molecular
Cristalografia por Raios X
Dissacarídeos/biossíntese
Escherichia coli/genética
Escherichia coli/metabolismo
Expressão Gênica
Cinética
Lactamas/metabolismo
Modelos Moleculares
Nucleotidiltransferases/genética
Nucleotidiltransferases/metabolismo
Ligação Proteica
Conformação Proteica em alfa-Hélice
Conformação Proteica em Folha beta
Domínios e Motivos de Interação entre Proteínas
Estrutura Terciária de Proteína
Proteínas Recombinantes/química
Proteínas Recombinantes/genética
Proteínas Recombinantes/metabolismo
Streptomyces/enzimologia
Homologia Estrutural de Proteína
Especificidade por Substrato
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Amino Acids, Diamino); 0 (Aminobutyrates); 0 (Anti-Bacterial Agents); 0 (Bacterial Proteins); 0 (Disaccharides); 0 (Lactams); 0 (Recombinant Proteins); 0 (cremimycin); 0 (incednine); EC 2.7.7.- (Nucleotidyltransferases)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170728
[Lr] Data última revisão:
170728
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170320
[St] Status:MEDLINE
[do] DOI:10.1002/prot.25284


  4 / 1132 MEDLINE  
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[PMID]:28264526
[Au] Autor:Xu Q; Liu F; Chen P; Jez JM; Krishnan HB
[Ad] Endereço:College of Life Sciences, Northwest A&F University, Yangling 712100, Shaanxi, China. xuql03@163.com.
[Ti] Título:ß-N-Oxalyl-l-α,ß-diaminopropionic Acid (ß-ODAP) Content in Lathyrus sativus: The Integration of Nitrogen and Sulfur Metabolism through ß-Cyanoalanine Synthase.
[So] Source:Int J Mol Sci;18(3), 2017 Feb 28.
[Is] ISSN:1422-0067
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:Grass pea ( L.) is an important legume crop grown mainly in South Asia and Sub-Saharan Africa. This underutilized legume can withstand harsh environmental conditions including drought and flooding. During drought-induced famines, this protein-rich legume serves as a food source for poor farmers when other crops fail under harsh environmental conditions; however, its use is limited because of the presence of an endogenous neurotoxic nonprotein amino acid ß- -oxalyl-l-α,ß-diaminopropionic acid (ß-ODAP). Long-term consumption of and ß-ODAP is linked to lathyrism, which is a degenerative motor neuron syndrome. Pharmacological studies indicate that nutritional deficiencies in methionine and cysteine may aggravate the neurotoxicity of ß-ODAP. The biosynthetic pathway leading to the production of ß-ODAP is poorly understood, but is linked to sulfur metabolism. To date, only a limited number of studies have been conducted in grass pea on the sulfur assimilatory enzymes and how these enzymes regulate the biosynthesis of ß-ODAP. Here, we review the current knowledge on the role of sulfur metabolism in grass pea and its contribution to ß-ODAP biosynthesis. Unraveling the fundamental steps and regulation of ß-ODAP biosynthesis in grass pea will be vital for the development of improved varieties of this underutilized legume.
[Mh] Termos MeSH primário: Diamino Aminoácidos/química
Diamino Aminoácidos/metabolismo
Lathyrus/química
Lathyrus/metabolismo
[Mh] Termos MeSH secundário: Vias Biossintéticas
Clonagem Molecular
Cisteína Sintase/genética
Cisteína Sintase/metabolismo
Expressão Gênica
Estudos de Associação Genética
Sulfeto de Hidrogênio/metabolismo
Lathyrus/genética
Liases/genética
Liases/metabolismo
Nitrogênio/metabolismo
Estresse Oxidativo
Melhoramento Vegetal
Relação Estrutura-Atividade
Enxofre/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Amino Acids, Diamino); 1TG777QI25 (oxalyldiaminopropionic acid); 70FD1KFU70 (Sulfur); EC 2.5.1.47 (Cysteine Synthase); EC 4.- (Lyases); EC 4.4.1.9 (beta-cyanoalanine synthase); N762921K75 (Nitrogen); YY9FVM7NSN (Hydrogen Sulfide)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170308
[St] Status:MEDLINE


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[PMID]:28179004
[Au] Autor:Salar-García MJ; Bernal V; Pastor JM; Salvador M; Argandoña M; Nieto JJ; Vargas C; Cánovas M
[Ad] Endereço:Departamento de Bioquímica y Biología Molecular B e Inmunología, Facultad de Química, Universidad de Murcia, Campus Regional de Excelencia Internacional "Campus Mare Nostrum", 30100, Murcia, Spain.
[Ti] Título:Understanding the interplay of carbon and nitrogen supply for ectoines production and metabolic overflow in high density cultures of Chromohalobacter salexigens.
[So] Source:Microb Cell Fact;16(1):23, 2017 Feb 08.
[Is] ISSN:1475-2859
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: The halophilic bacterium Chromohalobacter salexigens has been proposed as promising cell factory for the production of the compatible solutes ectoine and hydroxyectoine. This bacterium has evolved metabolic adaptations to efficiently grow under high salt concentrations by accumulating ectoines as compatible solutes. However, metabolic overflow, which is a major drawback for the efficient conversion of biological feedstocks, occurs as a result of metabolic unbalances during growth and ectoines production. Optimal production of ectoines is conditioned by the interplay of carbon and nitrogen metabolisms. In this work, we set out to determine how nitrogen supply affects the production of ectoines. RESULTS: Chromohalobacter salexigens was challenged to grow in media with unbalanced carbon/nitrogen ratio. In C. salexigens, overflow metabolism and ectoines production are a function of medium composition. At low ammonium conditions, the growth rate decreased importantly, up to 80%. Shifts in overflow metabolism were observed when changing the C/N ratio in the culture medium. C-NMR analysis of ectoines labelling revealed a high metabolic rigidity, with almost constant flux ratios in all conditions assayed. Unbalanced C/N ratio led to pyruvate accumulation, especially upon N-limitation. Analysis of an ect mutant demonstrated the link between metabolic overflow and ectoine biosynthesis. Under non ectoine synthesizing conditions, glucose uptake and metabolic overflow decreased importantly. Finally, in fed-batch cultures, biomass yield was affected by the feeding scheme chosen. High growth (up to 42.4 g L ) and volumetric ectoine yields (up to 4.21 g L ) were obtained by minimizing metabolite overflow and nutrient accumulation in high density cultures in a low nitrogen fed-batch culture. Moreover, the yield coefficient calculated for the transformation of glucose into biomass was 30% higher in fed-batch than in the batch culture, demonstrating that the metabolic efficiency of C. salexigens can be improved by careful design of culture feeding schemes. CONCLUSIONS: Metabolic shifts observed at low ammonium concentrations were explained by a shift in the energy required for nitrogen assimilation. Carbon-limited fed-batch cultures with reduced ammonium supply were the best conditions for cultivation of C. salexigens, supporting high density growth and maintaining high ectoines production.
[Mh] Termos MeSH primário: Diamino Aminoácidos/biossíntese
Carbono/metabolismo
Chromohalobacter/metabolismo
Nitrogênio/metabolismo
[Mh] Termos MeSH secundário: Amônia/farmacologia
Técnicas de Cultura Celular por Lotes
Biomassa
Metabolismo dos Carboidratos
Chromohalobacter/efeitos dos fármacos
Chromohalobacter/crescimento & desenvolvimento
Meios de Cultura/química
Glucose/metabolismo
Pressão Osmótica
Ácido Pirúvico/análise
Salinidade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Amino Acids, Diamino); 0 (Culture Media); 7440-44-0 (Carbon); 7664-41-7 (Ammonia); 7GXZ3858RY (ectoine); 8558G7RUTR (Pyruvic Acid); IY9XDZ35W2 (Glucose); N762921K75 (Nitrogen)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:170424
[Lr] Data última revisão:
170424
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170210
[St] Status:MEDLINE
[do] DOI:10.1186/s12934-017-0643-7


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[PMID]:28174119
[Au] Autor:Andersson M; Ersson L; Brandt I; Bergström U
[Ad] Endereço:Department of Environmental Toxicology, Uppsala University, Norbyvägen 18A, SE-752 36 Uppsala, Sweden.
[Ti] Título:Potential transfer of neurotoxic amino acid ß-N-methylamino-alanine (BMAA) from mother to infant during breast-feeding: Predictions from human cell lines.
[So] Source:Toxicol Appl Pharmacol;320:40-50, 2017 Apr 01.
[Is] ISSN:1096-0333
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:ß-N-methylamino-alanine (BMAA) is a non-protein amino acid produced by cyanobacteria, diatoms and dinoflagellates. BMAA has potential to biomagnify in a terrestrial food chain, and to bioaccumulate in fish and shellfish. We have reported that administration of [ C]l-BMAA to lactating mice and rats results in a mother to off-spring transfer via the milk. A preferential enantiomer-specific uptake of [ C]l-BMAA has also been demonstrated in differentiated murine mammary epithelium HC11 cells. These findings, together with neurotoxic effects of BMAA demonstrated both in vitro and in vivo, highlight the need to determine whether such transfer could also occur in humans. Here, we used four cell lines of human origin to examine and compare the transport of the two BMAA enantiomers in vitro. The uptake patterns of [ C]l- and [ C]d-BMAA in the human mammary MCF7 cell line were in agreement with the results in murine HC11 cells, suggesting a potential secretion of BMAA into human breast milk. The permeability coefficients for both [ C]l- and [ C]d-BMAA over monolayers of human intestinal Caco2 cells supported an efficient absorption from the human intestine. As a final step, transport experiments confirmed that [ C]l-and [ C]d-BMAA can be taken up by human SHSY5Y neuroblastoma cells and even more efficiently by human U343 glioblastoma cells. In competition experiments with various amino acids, the ASCT2 specific inhibitor benzylserine was the most effective inhibitor of [ C]l-BMAA uptake tested here. Altogether, our results suggest that BMAA can be transferred from an exposed mother, via the milk, to the brain of the nursed infant.
[Mh] Termos MeSH primário: Diamino Aminoácidos/metabolismo
Aleitamento Materno/efeitos adversos
Agonistas de Aminoácidos Excitatórios/metabolismo
Lactação/metabolismo
Exposição Materna/efeitos adversos
[Mh] Termos MeSH secundário: Diamino Aminoácidos/toxicidade
Animais
Transporte Biológico/efeitos dos fármacos
Transporte Biológico/fisiologia
Células CACO-2
Diferenciação Celular/efeitos dos fármacos
Diferenciação Celular/fisiologia
Linhagem Celular
Relação Dose-Resposta a Droga
Agonistas de Aminoácidos Excitatórios/toxicidade
Feminino
Previsões
Seres Humanos
Recém-Nascido
Lactação/efeitos dos fármacos
Células MCF-7
Camundongos
Mães
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Amino Acids, Diamino); 0 (Excitatory Amino Acid Agonists); 108SA6URTV (beta-N-methylamino-L-alanine)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170531
[Lr] Data última revisão:
170531
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170209
[St] Status:MEDLINE


  7 / 1132 MEDLINE  
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[PMID]:27956354
[Au] Autor:Karlsson O; Michno W; Ransome Y; Hanrieder J
[Ad] Endereço:Center for Molecular Medicine, Department of Clinical Neuroscience, Karolinska Institute, 171 76 Stockholm, Sweden; Department of Pharmaceutical Biosciences, Toxicology and Drug Safety, Uppsala University, Box 591, 751 24 Uppsala, Sweden; Department of Environmental Health, Harvard T.H. Chan School
[Ti] Título:MALDI imaging delineates hippocampal glycosphingolipid changes associated with neurotoxin induced proteopathy following neonatal BMAA exposure.
[So] Source:Biochim Biophys Acta;1865(7):740-746, 2017 07.
[Is] ISSN:0006-3002
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:The environmental toxin ß-N-methylamino-L-alanine (BMAA) has been proposed to contribute to neurodegenerative diseases. We have previously shown that neonatal exposure to BMAA results in dose-dependent cognitive impairments, proteomic alterations and progressive neurodegeneration in the hippocampus of adult rats. A high BMAA dose (460mg/kg) also induced intracellular fibril formation, increased protein ubiquitination and enrichment of proteins important for lipid transport and metabolism. The aim of this study was therefore to elucidate the role of neuronal lipids in BMAA-induced neurodegeneration. By using matrix assisted laser desorption/ionization imaging mass spectrometry (MALDI IMS), we characterized the spatial lipid profile in the hippocampus of six month-old rats that were treated neonatally (postnatal days 9-10) with 460mg/kg BMAA. Multivariate statistical analysis revealed long-term changes in distinct ganglioside species (GM, GD, GT) in the dentate gyrus. These changes could be a consequence of direct effects on ganglioside biosynthesis through the b-series (GM3-GD3-GD2-GD1b-GT1b) and may be linked to astrogliosis. Complementary immunohistochemistry experiments towards GFAP and S100ß further verified the role of increased astrocyte activity in BMAA-induced brain damage. This highlights the potential of imaging MS for probing chemical changes associated with neuropathological mechanisms in situ. This article is part of a Special Issue entitled: MALDI Imaging, edited by Dr. Corinna Henkel and Prof. Peter Hoffmann.
[Mh] Termos MeSH primário: Glicoesfingolipídeos/metabolismo
Hipocampo/metabolismo
Hipocampo/patologia
Neurotoxinas/toxicidade
[Mh] Termos MeSH secundário: Diamino Aminoácidos/toxicidade
Animais
Animais Recém-Nascidos
Astrócitos/efeitos dos fármacos
Astrócitos/metabolismo
Astrócitos/patologia
Giro Denteado/efeitos dos fármacos
Giro Denteado/metabolismo
Giro Denteado/patologia
Feminino
Gangliosídeos/metabolismo
Gliose/induzido quimicamente
Gliose/metabolismo
Gliose/patologia
Hipocampo/efeitos dos fármacos
Metabolismo dos Lipídeos/efeitos dos fármacos
Metabolismo dos Lipídeos/fisiologia
Lipídeos/fisiologia
Doenças Neurodegenerativas/induzido quimicamente
Doenças Neurodegenerativas/metabolismo
Doenças Neurodegenerativas/patologia
Neurotoxinas/metabolismo
Gravidez
Proteômica/métodos
Ratos
Ratos Wistar
Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Amino Acids, Diamino); 0 (Gangliosides); 0 (Glycosphingolipids); 0 (Lipids); 0 (Neurotoxins); 108SA6URTV (beta-N-methylamino-L-alanine)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170926
[Lr] Data última revisão:
170926
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161214
[St] Status:MEDLINE


  8 / 1132 MEDLINE  
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[PMID]:27845233
[Au] Autor:Salmannejad F; Nafissi-Varcheh N
[Ad] Endereço:Department of Pharmaceutics, School of Pharmacy, Alborz University of Medical Sciences, Karaj, Iran; Department of Pharmaceutics, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address: Salmannejad.f@gmail.com.
[Ti] Título:Ectoine and hydroxyectoine inhibit thermal-induced aggregation and increase thermostability of recombinant human interferon Alfa2b.
[So] Source:Eur J Pharm Sci;97:200-207, 2017 Jan 15.
[Is] ISSN:1879-0720
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:This study is to investigate whether ectoines (ectoine and hydroxyectoine) can reduce aggregation of rhIFNα2b in aqueous solutions on thermal stress. The effect of thermal stress condition on the stability was therefore investigated using size exclusion-high performance liquid chromatography (SE-HPLC), different spectroscopic measurements, dynamic light scattering (DLS), electrophoresis, and differential scanning calorimetry (DSC). All experiments were performed in a sodium phosphate buffer system (100mM, pH7). The protein samples (100µg/ml) were incubated at 50°C for 14days in the absence or presence (1, 10, 20, and 100mM) of ectoines. In summary, thermal-induced aggregation was reduced in the presence of ectoines, regardless of the ectoines concentration in different periods of incubation time by analyzing with SE-HPLC and turbidity measurement. The inhibitory effect of ectoines on the aggregation was shown by other techniques used. The optimal ectoines concentration was 10mM for aggregation reduction, so samples containing of 10mM of ectoines were selected for further evaluation. Secondary structural and conformational stability increased in presence of ectoines as measured by far-UV circular dichroism and fluorescence spectroscopy, respectively. DSC showed slight increase in T of interferon in the presence of ectoines. Hydroxyectoine had superior protein-stabilizing properties than ectoine. In conclusion, this study demonstrates that ectoine and hydroxyectoine are highly effective excipients which can significantly reduce the thermal-induced aggregation of rhIFNα2b at low concentration.
[Mh] Termos MeSH primário: Diamino Aminoácidos/farmacologia
Temperatura Alta/efeitos adversos
Interferon-alfa
Agregados Proteicos/efeitos dos fármacos
[Mh] Termos MeSH secundário: Diamino Aminoácidos/química
Linhagem Celular
Estabilidade de Medicamentos
Seres Humanos
Interferon-alfa/fisiologia
Agregados Proteicos/fisiologia
Estabilidade Proteica/efeitos dos fármacos
Proteínas Recombinantes
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Amino Acids, Diamino); 0 (Interferon-alpha); 0 (Protein Aggregates); 0 (Recombinant Proteins); 0 (hydroxyectoine); 43K1W2T1M6 (interferon alfa-2b); 7GXZ3858RY (ectoine)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170523
[Lr] Data última revisão:
170523
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161116
[St] Status:MEDLINE


  9 / 1132 MEDLINE  
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[PMID]:27796937
[Au] Autor:D'Mello F; Braidy N; Marçal H; Guillemin G; Rossi F; Chinian M; Laurent D; Teo C; Neilan BA
[Ad] Endereço:School of Biotechnology and Biomolecular Sciences, The University of New South Wales, Sydney, NSW, 2052, Australia.
[Ti] Título:Cytotoxic Effects of Environmental Toxins on Human Glial Cells.
[So] Source:Neurotox Res;31(2):245-258, 2017 Feb.
[Is] ISSN:1476-3524
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Toxins produced by cyanobacteria and dinoflagellates have increasingly become a public health concern due to their degenerative effects on mammalian tissue and cells. In particular, emerging evidence has called attention to the neurodegenerative effects of the cyanobacterial toxin ß-N-methylamino-L-alanine (BMAA). Other toxins such as the neurotoxins saxitoxin and ciguatoxin, as well as the hepatotoxic microcystin, have been previously shown to have a range of effects upon the nervous system. However, the capacity of these toxins to cause neurodegeneration in human cells has not, to our knowledge, been previously investigated. This study aimed to examine the cytotoxic effects of BMAA, microcystin-LR (MC-LR), saxitoxin (STX) and ciguatoxin (CTX-1B) on primary adult human astrocytes. We also demonstrated that α-lipoate attenuated MC-LR toxicity in primary astrocytes and characterised changes in gene expression which could potentially be caused by these toxins in primary astrocytes. Herein, we are the first to show that all of these toxins are capable of causing physiological changes consistent with neurodegeneration in glial cells, via oxidative stress and excitotoxicity, leading to a reduction in cell proliferation culminating in cell death. In addition, MC-LR toxicity was reduced significantly in astrocytes-treated α-lipoic acid. While there were no significant changes in gene expression, many of the probes that were altered were associated with neurodegenerative disease pathogenesis. Overall, this is important in advancing our current understanding of the mechanism of toxicity of MC-LR on human brain function in vitro, particularly in the context of neurodegeneration.
[Mh] Termos MeSH primário: Diamino Aminoácidos/toxicidade
Astrócitos/efeitos dos fármacos
Astrócitos/metabolismo
Ciguatoxinas/toxicidade
Microcistinas/toxicidade
Saxitoxina/toxicidade
[Mh] Termos MeSH secundário: Cálcio/metabolismo
Proliferação Celular/efeitos dos fármacos
Expressão Gênica/efeitos dos fármacos
Seres Humanos
L-Lactato Desidrogenase/metabolismo
Microcistinas/antagonistas & inibidores
Degeneração Neural/induzido quimicamente
Cultura Primária de Células
Espécies Reativas de Oxigênio/metabolismo
Ácido Tióctico/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Amino Acids, Diamino); 0 (Microcystins); 0 (Reactive Oxygen Species); 108SA6URTV (beta-N-methylamino-L-alanine); 11050-21-8 (Ciguatoxins); 35523-89-8 (Saxitoxin); 73Y7P0K73Y (Thioctic Acid); EC 1.1.1.27 (L-Lactate Dehydrogenase); EQ8332842Y (cyanoginosin LR); SY7Q814VUP (Calcium)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171110
[Lr] Data última revisão:
171110
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161101
[St] Status:MEDLINE
[do] DOI:10.1007/s12640-016-9678-5


  10 / 1132 MEDLINE  
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[PMID]:27795315
[Au] Autor:Yu Q; Cai H; Zhang Y; He Y; Chen L; Merritt J; Zhang S; Dong Z
[Ad] Endereço:State Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
[Ti] Título:Negative Regulation of Ectoine Uptake and Catabolism in Sinorhizobium meliloti: Characterization of the EhuR Gene.
[So] Source:J Bacteriol;199(1), 2017 Jan 01.
[Is] ISSN:1098-5530
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Ectoine has osmoprotective effects on Sinorhizobium meliloti that differ from its effects in other bacteria. Ectoine does not accumulate in S. meliloti cells; instead, it is degraded. The products of the ehuABCD-eutABCDE operon were previously discovered to be responsible for the uptake and catabolism of ectoine in S. meliloti However, the mechanism by which ectoine is involved in the regulation of the ehuABCD-eutABCDE operon remains unclear. The ehuR gene, which is upstream of and oriented in the same direction as the ehuABCD-eutABCDE operon, encodes a member of the MocR/GntR family of transcriptional regulators. Quantitative reverse transcription-PCR and promoter-lacZ reporter fusion experiments revealed that EhuR represses transcription of the ehuABCD-eutABCDE operon, but this repression is inhibited in the presence of ectoine. Electrophoretic mobility shift assays and DNase I footprinting assays revealed that EhuR bound specifically to the DNA regions overlapping the -35 region of the ehuA promoter and the +1 region of the ehuR promoter. Surface plasmon resonance assays further demonstrated direct interactions between EhuR and the two promoters, although EhuR was found to have higher affinity for the ehuA promoter than for the ehuR promoter. In vitro, DNA binding by EhuR could be directly inhibited by a degradation product of ectoine. Our work demonstrates that EhuR is an important negative transcriptional regulator involved in the regulation of ectoine uptake and catabolism and is likely regulated by one or more end products of ectoine catabolism. IMPORTANCE: Sinorhizobium meliloti is an important soil bacterium that displays symbiotic interactions with legume hosts. Ectoine serves as a key osmoprotectant for S. meliloti However, ectoine does not accumulate in the cells; rather, it is degraded. In this study, we characterized the transcriptional regulation of the operon responsible for ectoine uptake and catabolism in S. meliloti We identified and characterized the transcription repressor EhuR, which is the first MocR/GntR family member found to be involved in the regulation of compatible solute uptake and catabolism. More importantly, we demonstrated for the first time that an ectoine catabolic end product could modulate EhuR DNA-binding activity. Therefore, this work provides new insights into the unique mechanism of ectoine-induced osmoprotection in S. meliloti.
[Mh] Termos MeSH primário: Diamino Aminoácidos/metabolismo
Proteínas de Bactérias/metabolismo
Regulação Bacteriana da Expressão Gênica/fisiologia
Sinorhizobium meliloti/metabolismo
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Proteínas de Bactérias/genética
Sequência de Bases
DNA Bacteriano/genética
Deleção de Genes
Osmorregulação
Regiões Promotoras Genéticas
Ligação Proteica
RNA Bacteriano/genética
RNA Bacteriano/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Amino Acids, Diamino); 0 (Bacterial Proteins); 0 (DNA, Bacterial); 0 (RNA, Bacterial); 7GXZ3858RY (ectoine)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170714
[Lr] Data última revisão:
170714
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161101
[St] Status:MEDLINE



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