Non-linear impact of glutathione depletion on C. elegans life span and stress resistance
| العنوان: | Non-linear impact of glutathione depletion on C. elegans life span and stress resistance |
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| المؤلفون: | Michael Ristow, Katrin Erler, Vanessa Stein, Dimitrios Tsitsipatis, Katrin Kreuzer, Nadine Urban, Lars-Oliver Klotz, Holger Steinbrenner, Franziska Hausig |
| المصدر: | Redox Biology, Vol 11, Iss, Pp 502-515 (2017) Redox Biology, 11 Redox Biology |
| بيانات النشر: | Elsevier BV, 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | 0301 basic medicine, GSSG, glutathione disulfide, Aging, Clinical Biochemistry, GPX, glutathione peroxidase, DMSO, dimethyl sulfoxide, FoxO1, forkhead box class O 1, medicine.disease_cause, Nrf2, nuclear factor erythroid 2-related factor 2, SKN-1, skinhead 1, Biochemistry, GST, glutathione S-transferase, chemistry.chemical_compound, PBST, phosphate-buffered saline with Tween 20, 0302 clinical medicine, TRXR, thioredoxin reductase, GSH, glutathione, NGM, nematode growth medium, lcsh:QH301-705.5, Maximum life span, GFP, green fluorescent protein, EGL, egg laying defective, lcsh:R5-920, Gene knockdown, Cell Death, E. coli, Escherichia coli, Gene Expression Regulation, Developmental, Forkhead Transcription Factors, Dipeptides, Glutathione, Cell biology, DNA-Binding Proteins, DEM, diethyl maleate, DAF-16, abnormal dauer formation 16, TRX, thioredoxin, Gene Knockdown Techniques, C. elegans, Thiol, lcsh:Medicine (General), Oxidation-Reduction, Intracellular, Research Paper, mBBr, monobromobimane, DTNB, 5,5'-dithiobis-(2-nitrobenzoic acid), Programmed cell death, Glutamate-Cysteine Ligase, Stress resistance, γ-glutamylcysteine synthetase, Hormesis, Biology, 03 medical and health sciences, ROS, reactive oxygen species, C. elegans, Caenorhabditis elegans, SOD, superoxide dismutase, Daf-16, medicine, Animals, Sulfhydryl Compounds, Caenorhabditis elegans, Caenorhabditis elegans Proteins, Organic Chemistry, Maleates, CTL, catalase, ICL, isocitrate lyase, BCA, bicinchoninic acid, Repressor Proteins, Oxidative Stress, 030104 developmental biology, lcsh:Biology (General), chemistry, Tumor Suppressor Protein p53, GCS, γ-glutamylcysteine synthetase, 030217 neurology & neurosurgery, Oxidative stress, Transcription Factors |
| الوصف: | 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. ISSN:2213-2317 Redox Biology, 11 |
| وصف الملف: | application/application/pdf |
| تدمد: | 2213-2317 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8d3d0f5a81c28796cc1effeb8046a536 https://doi.org/10.1016/j.redox.2016.12.003 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....8d3d0f5a81c28796cc1effeb8046a536 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 22132317 |
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