論文 - 詳細
| RRC ID | 76342 |
|---|---|
| 著者 | Zhao L, Fenk LA, Nilsson L, Amin-Wetzel NP, Ramirez-Suarez NJ, de Bono M, Chen C. |
| タイトル | ROS and cGMP signaling modulate persistent escape from hypoxia in Caenorhabditis elegans. |
| ジャーナル | PLoS Biol |
| Abstract |
The ability to detect and respond to acute oxygen (O2) shortages is indispensable to aerobic life. The molecular mechanisms and circuits underlying this capacity are poorly understood. Here, we characterize the behavioral responses of feeding Caenorhabditis elegans to approximately 1% O2. Acute hypoxia triggers a bout of turning maneuvers followed by a persistent switch to rapid forward movement as animals seek to avoid and escape hypoxia. While the behavioral responses to 1% O2 closely resemble those evoked by 21% O2, they have distinct molecular and circuit underpinnings. Disrupting phosphodiesterases (PDEs), specific G proteins, or BBSome function inhibits escape from 1% O2 due to increased cGMP signaling. A primary source of cGMP is GCY-28, the ortholog of the atrial natriuretic peptide (ANP) receptor. cGMP activates the protein kinase G EGL-4 and enhances neuroendocrine secretion to inhibit acute responses to 1% O2. Triggering a rise in cGMP optogenetically in multiple neurons, including AIA interneurons, rapidly and reversibly inhibits escape from 1% O2. Ca2+ imaging reveals that a 7% to 1% O2 stimulus evokes a Ca2+ decrease in several neurons. Defects in mitochondrial complex I (MCI) and mitochondrial complex I (MCIII), which lead to persistently high reactive oxygen species (ROS), abrogate acute hypoxia responses. In particular, repressing the expression of isp-1, which encodes the iron sulfur protein of MCIII, inhibits escape from 1% O2 without affecting responses to 21% O2. Both genetic and pharmacological up-regulation of mitochondrial ROS increase cGMP levels, which contribute to the reduced hypoxia responses. Our results implicate ROS and precise regulation of intracellular cGMP in the modulation of acute responses to hypoxia by C. elegans. |
| 巻・号 | 20(6) |
| ページ | e3001684 |
| 公開日 | 2022-6-1 |
| DOI | 10.1371/journal.pbio.3001684 |
| PII | PBIOLOGY-D-21-01767 |
| PMID | 35727855 |
| PMC | PMC9249223 |
| MeSH | Animals Caenorhabditis elegans* / metabolism Caenorhabditis elegans Proteins* / metabolism Calcium / metabolism Cyclic GMP / metabolism Cyclic GMP-Dependent Protein Kinases / genetics Cyclic GMP-Dependent Protein Kinases / metabolism Hypoxia Oxygen / metabolism Reactive Oxygen Species / metabolism |
| 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 | 10 |
| 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 | tm3098 tm3765 tm1146 tm783 tm760 |