論文 - 詳細
| RRC ID | 12159 |
|---|---|
| 著者 | Nishida M, Maruyama Y, Tanaka R, Kontani K, Nagao T, Kurose H. |
| タイトル | G alpha(i) and G alpha(o) are target proteins of reactive oxygen species. |
| ジャーナル | Nature |
| Abstract |
Reactive oxygen species (ROS) have been identified as central mediators in certain signalling events. In the heart, ROS have important functions in ischaemia/reperfusion-induced cardiac injury and in cytokine-stimulated hypertrophy. Extracellular signal-regulated kinase (ERK) is one of the ROS-responsive serine/threonine kinases. Previous studies showed that tyrosine kinases and small G proteins are involved in the activation of ERK by ROS; however, the initial target protein of ROS that leads to ERK activation remains unknown. Here we show that inhibition of the betagamma-subunit of G protein (G betagamma) attenuates hydrogen peroxide (H2O2)-induced ERK activation in rat neonatal cardiomyocytes. The G betagamma-responsive ERK activation induced by H2O2 is independent of ligands binding to Gi-coupled receptors, but requires phosphatidylinositol-3-kinase and Src activation. In in vitro studies, however, treatment with H2O2 increases [35S]GTP-gammaS binding to cardiac membranes and directly activates purified heterotrimeric Gi and Go but not Gs. Analysis using heterotrimeric Go and its individual subunits indicates that H2O2 modifies G alpha(o) but not G betagamma, which leads to subunit dissociation. We conclude that G alpha(i) and G alpha(o) are critical targets of oxidative stress for activation of ERK. |
| 巻・号 | 408(6811) |
| ページ | 492-5 |
| 公開日 | 2000-11-23 |
| DOI | 10.1038/35044120 |
| PMID | 11100733 |
| MeSH | Animals Cells, Cultured Cyclic AMP-Dependent Protein Kinases / metabolism Enzyme Activation GTP-Binding Protein alpha Subunits, Gi-Go / metabolism GTP-Binding Proteins / metabolism* Guanosine 5'-O-(3-Thiotriphosphate) / metabolism Heterotrimeric GTP-Binding Proteins / metabolism Hydrogen Peroxide / metabolism Mitogen-Activated Protein Kinases / metabolism Myocardium / metabolism Oxidative Stress Protein Structure, Tertiary Rats Rats, Sprague-Dawley Reactive Oxygen Species / metabolism* Virulence Factors, Bordetella / pharmacology beta-Adrenergic Receptor Kinases |
| IF | 42.779 |
| 引用数 | 207 |
| 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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| 各媒体での言及数の合計 | 0 |
| リソース情報 | |
| 遺伝子材料 | AxCALacZ Adex1CAlacZ (RDB02726) |