論文 - 詳細
| RRC ID | 58147 |
|---|---|
| 著者 | Horsman JW, Heinis FI, Miller DL. |
| タイトル | A Novel Mechanism To Prevent H2S Toxicity in Caenorhabditis elegans. |
| ジャーナル | Genetics |
| Abstract |
Hydrogen sulfide (H2S) is an endogenously produced signaling molecule that can be cytoprotective, especially in conditions of ischemia/reperfusion injury. However, H2S is also toxic, and unregulated accumulation or exposure to environmental H2S can be lethal. In Caenorhabditis elegans, the hypoxia inducible factor (hif-1) coordinates the initial transcriptional response to H2S, and is essential to survive exposure to low concentrations of H2S. We performed a forward genetic screen to identify mutations that suppress the lethality of hif-1 mutant animals in H2S. The mutations we recovered are specific for H2S, as they do not suppress embryonic lethality or reproductive arrest of hif-1 mutant animals in hypoxia, nor can they prevent the death of hif-1 mutant animals exposed to hydrogen cyanide. The majority of hif-1 suppressor mutations we recovered activate the skn-1/Nrf2 transcription factor. Activation of SKN-1 by hif-1 suppressor mutations increased the expression of a subset of H2S-responsive genes, consistent with previous findings that skn-1 plays a role in the transcriptional response to H2S. Using transgenic rescue, we show that overexpression of a single gene, rhy-1, is sufficient to protect hif-1 mutant animals in H2S. The rhy-1 gene encodes a predicated O-acyltransferase enzyme that has previously been shown to negatively regulate HIF-1 activity. Our data indicate that RHY-1 has novel, hif-1 independent, function that promotes survival in H2S. |
| 巻・号 | 213(2) |
| ページ | 481-490 |
| 公開日 | 2019-10-1 |
| DOI | 10.1534/genetics.119.302326 |
| PII | genetics.119.302326 |
| PMID | 31371406 |
| PMC | PMC6781907 |
| MeSH | Acyltransferases / genetics* Animals Caenorhabditis elegans / drug effects Caenorhabditis elegans / genetics* Caenorhabditis elegans Proteins / genetics* DNA-Binding Proteins / genetics Gene Expression Regulation / drug effects Green Fluorescent Proteins / genetics Hydrogen Cyanide / toxicity Hydrogen Sulfide / metabolism Hydrogen Sulfide / toxicity* Hypoxia / genetics Hypoxia / metabolism Mutation Synthetic Lethal Mutations / drug effects Transcription Factors / genetics* |
| IF | 4.015 |
| 引用数 | 2 |
| 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 | 16 |
| 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 | tm3378 |