Gα12/13- and Reactive Oxygen Species-dependent Activation of c-Jun NH2-terminal Kinase and p38 Mitogen-activated Protein Kinase by Angiotensin Receptor Stimulation in Rat Neonatal Cardiomyocytes
| Autor: | Taku Nagao, Justin H. Turner, Tohru Kozasa, Yuichi Nagamatsu, Kyoji Urayama, Yoji Sato, Motohiro Nishida, Toru Kawanishi, Ryuji Inoue, Supachoke Mangmool, Yoshiko Maruyama, Shihori Tanabe, Hitoshi Kurose, Hiroyuki Kobayashi, Shuichi Takagahara |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
MAPK/ERK pathway
Angiotensin receptor p38 mitogen-activated protein kinases Tetrazoles Mitogen-activated protein kinase kinase GTP-Binding Protein alpha Subunits G12-G13 p38 Mitogen-Activated Protein Kinases Biochemistry Rats Sprague-Dawley Angiotensin Receptor Antagonists Mice Animals Myocytes Cardiac Molecular Biology Rho-associated protein kinase Receptors Angiotensin MAP kinase kinase kinase Chemistry Kinase Biphenyl Compounds JNK Mitogen-Activated Protein Kinases Cell Biology Rats Cell biology Enzyme Activation Animals Newborn Rho kinase inhibitor Benzimidazoles sense organs Reactive Oxygen Species |
| Zdroj: | Journal of Biological Chemistry. 280:18434-18441 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m409710200 |
| Popis: | In the present study, we examined signal transduction mechanism of reactive oxygen species (ROS) production and the role of ROS in angiotensin II-induced activation of mitogen-activated protein kinases (MAPKs) in rat neonatal cardiomyocytes. Among three MAPKs, c-Jun NH(2)-terminal kinase (JNK) and p38 MAPK required ROS production for activation, as an NADPH oxidase inhibitor, diphenyleneiodonium, inhibited the activation. The angiotensin II-induced activation of JNK and p38 MAPK was also inhibited by the expression of the Galpha(12/13)-specific regulator of G protein signaling (RGS) domain, a specific inhibitor of Galpha(12/13), but not by an RGS domain specific for Galpha(q). Constitutively active Galpha(12)- or Galpha(13)-induced activation of JNK and p38 MAPK, but not extracellular signal-regulated kinase (ERK), was inhibited by diphenyleneiodonium. Angiotensin II receptor stimulation rapidly activated Galpha(13), which was completely inhibited by the Galpha(12/13)-specific RGS domain. Furthermore, the Galpha(12/13)-specific but not the Galpha(q)-specific RGS domain inhibited angiotensin II-induced ROS production. Dominant negative Rac inhibited angiotensin II-stimulated ROS production, JNK activation, and p38 MAPK activation but did not affect ERK activation. Rac activation was mediated by Rho and Rho kinase, because Rac activation was inhibited by C3 toxin and a Rho kinase inhibitor, Y27632. Furthermore, angiotensin II-induced Rho activation was inhibited by Galpha(12/13)-specific RGS domain but not dominant negative Rac. An inhibitor of epidermal growth factor receptor kinase AG1478 did not affect angiotensin II-induced JNK activation cascade. These results suggest that Galpha(12/13)-mediated ROS production through Rho and Rac is essential for JNK and p38 MAPK activation. |
| Databáze: | OpenAIRE |
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