RRC ID 2016
著者 Nishida M, Tanabe S, Maruyama Y, Mangmool S, Urayama K, Nagamatsu Y, Takagahara S, Turner JH, Kozasa T, Kobayashi H, Sato Y, Kawanishi T, Inoue R, Nagao T, Kurose H.
タイトル G alpha 12/13- 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.
ジャーナル J Biol Chem
Abstract 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.
巻・号 280(18)
ページ 18434-41
公開日 2005-5-6
DOI 10.1074/jbc.M409710200
PII S0021-9258(20)65796-9
PMID 15743761
MeSH Angiotensin Receptor Antagonists Animals Animals, Newborn Benzimidazoles / pharmacology Biphenyl Compounds Enzyme Activation / drug effects Enzyme Activation / physiology GTP-Binding Protein alpha Subunits, G12-G13 / antagonists & inhibitors GTP-Binding Protein alpha Subunits, G12-G13 / physiology* JNK Mitogen-Activated Protein Kinases / metabolism* Mice Myocytes, Cardiac / drug effects Myocytes, Cardiac / metabolism* Rats Rats, Sprague-Dawley Reactive Oxygen Species / antagonists & inhibitors Reactive Oxygen Species / metabolism* Receptors, Angiotensin / physiology* Tetrazoles / pharmacology p38 Mitogen-Activated Protein Kinases / metabolism*
IF 4.238
引用数 110
WOS 分野 BIOCHEMISTRY & MOLECULAR BIOLOGY
リソース情報
遺伝子材料 AxCALacZ (RDB01745)