論文 - 詳細
| RRC ID | 46069 |
|---|---|
| 著者 | Lüersen K, Stegehake D, Daniel J, Drescher M, Ajonina I, Ajonina C, Hertel P, Woltersdorf C, Liebau E. |
| タイトル | The glutathione reductase GSR-1 determines stress tolerance and longevity in Caenorhabditis elegans. |
| ジャーナル | PLoS One |
| Abstract |
Glutathione (GSH) and GSH-dependent enzymes play a key role in cellular detoxification processes that enable organism to cope with various internal and environmental stressors. However, it is often not clear, which components of the complex GSH-metabolism are required for tolerance towards a certain stressor. To address this question, a small scale RNAi-screen was carried out in Caenorhabditis elegans where GSH-related genes were systematically knocked down and worms were subsequently analysed for their survival rate under sub-lethal concentrations of arsenite and the redox cycler juglone. While the knockdown of γ-glutamylcysteine synthetase led to a diminished survival rate under arsenite stress conditions, GSR-1 (glutathione reductase) was shown to be essential for survival under juglone stress conditions. gsr-1 is the sole GSR encoding gene found in C. elegans. Knockdown of GSR-1 hardly affected total glutathione levels nor reduced glutathione/glutathione disulphide (GSH/GSSG) ratio under normal laboratory conditions. Nevertheless, when GSSG recycling was impaired by gsr-1(RNAi), GSH synthesis was induced, but not vice versa. Moreover, the impact of GSSG recycling was potentiated under oxidative stress conditions, explaining the enormous effect gsr-1(RNAi) knockdown had on juglone tolerance. Accordingly, overexpression of GSR-1 was capable of increasing stress tolerance. Furthermore, expression levels of SKN-1-regulated GSR-1 also affected life span of C. elegans, emphasising the crucial role the GSH redox state plays in both processes. |
| 巻・号 | 8(4) |
| ページ | e60731 |
| 公開日 | 2013-1-1 |
| DOI | 10.1371/journal.pone.0060731 |
| PII | PONE-D-12-27450 |
| PMID | 23593298 |
| PMC | PMC3620388 |
| MeSH | Animals Arsenites / toxicity Caenorhabditis elegans / drug effects Caenorhabditis elegans / enzymology* Caenorhabditis elegans / metabolism Caenorhabditis elegans / physiology* Caenorhabditis elegans Proteins / metabolism Gene Expression Regulation, Enzymologic / drug effects Gene Knockdown Techniques Glutathione / metabolism Glutathione Reductase / deficiency Glutathione Reductase / genetics Glutathione Reductase / metabolism* Longevity* / drug effects Naphthoquinones / toxicity Oxidants / toxicity Oxidation-Reduction / drug effects Oxidative Stress* / drug effects Phenotype RNA Interference Stress, Physiological / drug effects |
| IF | 2.74 |
| 引用数 | 25 |
| WOS 分野 | BIOCHEMISTRY & MOLECULAR BIOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 2 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 線虫 | tm3574 |