論文 - 詳細
| RRC ID | 53409 |
|---|---|
| 著者 | Livshits L, Chatterjee AK, Karbian N, Abergel R, Abergel Z, Gross E. |
| タイトル | Mechanisms of defense against products of cysteine catabolism in the nematode Caenorhabditis elegans. |
| ジャーナル | Free Radic Biol Med |
| Abstract |
Cysteine catabolism presents cells with a double-edged sword. On the one hand, cysteine degradation provides cells with essential molecules such as taurine and sulfide. The formation of sulfide in cells is thought to regulate important and diverse physiological processes including blood circulation, synaptic activity and inflammation. On the other hand, the catabolism of cysteine by gut microbiota can release high levels of sulfide that may underlie the development or relapse of ulcerative colitis, an inflammatory bowel disease affecting millions of people worldwide. Here, we have used the nematode C. elegans to explore how cells tolerate high levels of sulfide produced by cysteine degradation in bacteria. We have identified mutations in genes coding for thioredoxin family proteins, mitochondrial proteins, and collagens that confer tolerance to sulfide toxicity. Exposure to sulfide induces the unfolded protein response in the endoplasmic reticulum and mitochondria. Moreover, our results suggest that sulfide toxicity is mediated by reactive oxygen species (ROS). Indeed, pre-treatment of worms with antioxidants increases their tolerance to sulfide toxicity. Intriguingly, sub-toxic levels of the superoxide generator paraquat can also increase the tolerance of worms to sulfide. Therefore, it appears that activation of ROS detoxification pathway prior to the exposure to sulfide, can increase the tolerance to sulfide toxicity. Our results suggest that these detoxification pathways are mediated by the hypoxia inducible factor HIF-1. Finally, we show that sulfide resistance varies among wild C. elegans and other nematode species, suggesting that tolerance to sulfide was naturally selected in certain habitats. |
| 巻・号 | 104 |
| ページ | 346-359 |
| 公開日 | 2017-3-1 |
| DOI | 10.1016/j.freeradbiomed.2017.02.007 |
| PII | S0891-5849(17)30068-0 |
| PMID | 28179109 |
| MeSH | Animals Antioxidants / administration & dosage Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / genetics* Caenorhabditis elegans Proteins / metabolism Cysteine / metabolism* Endoplasmic Reticulum / drug effects Endoplasmic Reticulum / pathology Gastrointestinal Microbiome / genetics Hydrogen Sulfide / metabolism Longevity / drug effects* Longevity / genetics Metabolism Mitochondria / drug effects Mitochondria / pathology Mutation Paraquat / administration & dosage Reactive Oxygen Species / metabolism Sulfides / metabolism* Sulfides / toxicity Transcription Factors / genetics* Transcription Factors / metabolism |
| IF | 6.17 |
| 引用数 | 3 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 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 | NA |