Gαi and Gαo are target proteins of reactive oxygen species

Motohiro Nishida, Yoshiko Maruyama, Rie Tanaka, Kenji Kontani, Taku Nagao and Hitoshi Kurose ()
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Motohiro Nishida: Laboratory of Pharmacology and Toxicology
Yoshiko Maruyama: Laboratory of Pharmacology and Toxicology
Rie Tanaka: Laboratory of Pharmacology and Toxicology
Kenji Kontani: Laboratory of Physiological Chemistry, Graduate School of Pharmaceutical Science, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku
Taku Nagao: Laboratory of Pharmacology and Toxicology
Hitoshi Kurose: Laboratory of Pharmacology and Toxicology

Nature, 2000, vol. 408, issue 6811, 492-495

Abstract: Abstract Reactive oxygen species (ROS) have been identified as central mediators in certain signalling events1,2,3,4. In the heart, ROS have important functions in ischaemia/reperfusion-induced cardiac injury5,6 and in cytokine-stimulated hypertrophy7. 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 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 Gi-coupled receptors, but requires phosphatidylinositol-3-kinase and Src activation. In in vitro studies, however, treatment with H2O2 increases [35S]GTP-γS 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 Gαo but not Gβγ, which leads to subunit dissociation. We conclude that Gαi and Gαo are critical targets of oxidative stress for activation of ERK.

Date: 2000
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DOI: 10.1038/35044120

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