Gα(i) and Gα(o) are target proteins of reactive oxygen species

Motohiro Nishida, Yoshiko Maruyama, Rie Tanaka, Kenji Kontani, Taku Nagao, Hitoshi Kurose

研究成果: Contribution to journalArticle査読

223 被引用数 (Scopus)

抄録

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 βγ-subunit of G protein (Gβγ) attenuates hydrogen peroxide (H2O2)-induced ERK activation in rat neonatal cardiomyocytes. The Gβγ-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 [35S]GTPγS 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 Gα(o) but not Gβγ, which leads to subunit dissociation. We conclude that Gα(i) and Gα(o) are critical targets of oxidative stress for activation of ERK.

本文言語英語
ページ(範囲)492-495
ページ数4
ジャーナルNature
408
6811
DOI
出版ステータス出版済み - 11 23 2000
外部発表はい

All Science Journal Classification (ASJC) codes

  • General

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