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

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

Research output: Contribution to journalArticle

214 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)492-495
Number of pages4
JournalNature
Volume408
Issue number6811
DOIs
Publication statusPublished - Nov 23 2000
Externally publishedYes

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Gi-Go GTP-Binding Protein alpha Subunits
Extracellular Signal-Regulated MAP Kinases
Reactive Oxygen Species
Phosphatidylinositol 3-Kinase
Monomeric GTP-Binding Proteins
Protein-Serine-Threonine Kinases
GTP-Binding Proteins
Cardiac Myocytes
Protein-Tyrosine Kinases
Hypertrophy
Hydrogen Peroxide
Reperfusion
Oxidative Stress
Ischemia
Cytokines
Ligands
Membranes
Wounds and Injuries

All Science Journal Classification (ASJC) codes

  • General

Cite this

Gα(i) and Gα(o) are target proteins of reactive oxygen species. / Nishida, Motohiro; Maruyama, Yoshiko; Tanaka, Rie; Kontani, Kenji; Nagao, Taku; Kurose, Hitoshi.

In: Nature, Vol. 408, No. 6811, 23.11.2000, p. 492-495.

Research output: Contribution to journalArticle

Nishida, M, Maruyama, Y, Tanaka, R, Kontani, K, Nagao, T & Kurose, H 2000, 'Gα(i) and Gα(o) are target proteins of reactive oxygen species', Nature, vol. 408, no. 6811, pp. 492-495. https://doi.org/10.1038/35044120
Nishida, Motohiro ; Maruyama, Yoshiko ; Tanaka, Rie ; Kontani, Kenji ; Nagao, Taku ; Kurose, Hitoshi. / Gα(i) and Gα(o) are target proteins of reactive oxygen species. In: Nature. 2000 ; Vol. 408, No. 6811. pp. 492-495.
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