کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8287306 | 1535839 | 2017 | 38 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Non-linear impact of glutathione depletion on C. elegans life span and stress resistance
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کلمات کلیدی
GCsGPXFOXO1PBSTC. elegansBCADTNBMBBRNGMEGLGSSGTrxTrxRICLDAF-16DemSKN-1phosphate-buffered saline with Tween 205,5'-dithiobis-(2-nitrobenzoic acid)egg laying defectiveGSTE. coliCTLGFPNrf2GSHDMSO - DMSOROS - ROSγ-glutamylcysteine synthetase - γ-گلوتامیل سستئین سینتاتازEscherichia coli - اشریشیا کُلیIsocitrate lyase - ایزوسیترات لیائازbicinchoninic acid - بیسینکنینیک اسیدthioredoxin reductase - تریودوکسین ردوکتازthioredoxin - تیرودوکسینThiol - تیول، مرکاپتانdiethyl maleate - دی اتیل مولاناDimethyl sulfoxide - دیمتیل سولفواکسیدnematode growth medium - رشد متوسط نماتدAging - سالخوردگیSOD - سدSuperoxide dismutase - سوکسوکس دیسموتازnuclear factor erythroid 2-related factor 2 - فاکتور هسته ای عامل erythroid 2 مرتبط 2Stress resistance - مقاومت در برابر استرسMonobromobimane - مونوبرموبیمنHormesis - هورمسیسgreen fluorescent protein - پروتئین فلورسنت سبزCatalase - کاتالازCaenorhabditis elegans - کرم الگانس Glutathione - گلوتاتیونglutathione S-transferase - گلوتاتیون S-ترانسفرازglutathione disulfide - گلوتاتیون دی سولفیدglutathione peroxidase - گلوتاتیون پراکسیدازReactive oxygen species - گونههای فعال اکسیژن
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
سالمندی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
The redox environment in cells and organisms is set by low-molecular mass and protein-bound thiols, with glutathione (GSH) representing a major intracellular redox buffer. Subtle thiol oxidation elicits signal transduction processes and adaptive responses to cope with stressors, whereas highly oxidizing conditions may provoke cell death. We here tested how thiol depletion affects life span, stress resistance and stress signaling in the model organism Caenorhabditis elegans. Diethyl maleate (DEM), an α,β-unsaturated carbonyl compound that conjugates to GSH and other thiols, decreased C. elegans life span at a concentration of 1 mM. In contrast, low and moderate doses of DEM (10-100 µM) increased mean and maximum life span and improved resistance against oxidative stress. DEM-induced life span extension was not detectable in worms deficient in either the FoxO orthologue, DAF-16, or the Nrf2 orthologue, SKN-1, pointing to a collaborative role of the two transcription factors in life span extension induced by thiol depletion. Cytoprotective target genes of DAF-16 and SKN-1 were upregulated after at least 3 days of exposure to 100 µM DEM, but not 1 mM DEM, whereas only 1 mM DEM caused upregulation of egl-1, a gene controlled by a p53-orthologue, CEP-1. In order to test whether depletion of GSH may elicit effects similar to DEM, we suppressed GSH biosynthesis in worms by attenuating γ-glutamylcysteine synthetase (gcs-1) expression through RNAi. The decline in GSH levels elicited by gcs-1 knockdown starting at young adult stage did not impair viability, but increased both stress resistance and life expectancy of the worms. In contrast, gcs-1 knockdown commencing right after hatching impaired nematode stress resistance and rendered young adult worms prone to vulval ruptures during egg-laying. Thus, modest decrease in GSH levels in young adult worms may promote stress resistance and life span, whereas depletion of GSH is detrimental to freshly hatched and developing worms.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Redox Biology - Volume 11, April 2017, Pages 502-515
Journal: Redox Biology - Volume 11, April 2017, Pages 502-515
نویسندگان
Nadine Urban, Dimitrios Tsitsipatis, Franziska Hausig, Katrin Kreuzer, Katrin Erler, Vanessa Stein, Michael Ristow, Holger Steinbrenner, Lars-Oliver Klotz,