Gαi and Gαo are target proteins of reactive oxygen species

被引:218
作者
Nishida, M
Maruyama, Y
Tanaka, R
Kontani, K
Nagao, T
Kurose, H
机构
[1] Univ Tokyo, Grad Sch Pharmaceut Sci, Lab Pharmacol & Toxicol, Bunkyo Ku, Tokyo 1130033, Japan
[2] Univ Tokyo, Grad Sch Pharmaceut Sci, Physiol Chem Lab, Bunkyo Ku, Tokyo 1130033, Japan
关键词
D O I
10.1038/35044120
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Reactive oxygen species (ROS) have been identified as central mediators in certain signalling events(1-4). In the heart, ROS have important functions in ischaemia/reperfusion-induced cardiac injury(5,6) and in cytokine-stimulated hypertrophy(7). 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 ROS4,8; however, the initial target protein of ROS that leads to ERK activation remains unknown. Here we show that inhibition of the beta gamma -subunit of G protein (G beta gamma) attenuates hydrogen peroxide (H2O2)-induced ERK activation in rat neonatal cardiomyocytes. The G beta gamma -responsive ERK activation induced by H2O2 is independent of ligands binding to G(i)-coupled receptors, but requires phosphatidylinositol-3-kinase and Src activation. In in vitro studies, however, treatment with H2O2 increases [S-35]GTP-gammaS binding to cardiac membranes and directly activates purified heterotrimeric G(i) and G(o) but not G(s). Analysis using heterotrimeric G(o) and its individual subunits indicates that H2O2 modifies G alpha (o) but not G beta gamma, 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.
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页码:492 / 495
页数:5
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