RRC ID 12159
Author Nishida M, Maruyama Y, Tanaka R, Kontani K, Nagao T, Kurose H.
Title G alpha(i) and G alpha(o) are target proteins of reactive oxygen species.
Journal Nature
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 betagamma-subunit of G protein (G betagamma) attenuates hydrogen peroxide (H2O2)-induced ERK activation in rat neonatal cardiomyocytes. The G betagamma-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-gammaS 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 G alpha(o) but not G betagamma, 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.
Volume 408(6811)
Pages 492-5
Published 2000-11-23
DOI 10.1038/35044120
PMID 11100733
MeSH Animals Cells, Cultured Cyclic AMP-Dependent Protein Kinases / metabolism Enzyme Activation GTP-Binding Protein alpha Subunits, Gi-Go / metabolism GTP-Binding Proteins / metabolism* Guanosine 5'-O-(3-Thiotriphosphate) / metabolism Heterotrimeric GTP-Binding Proteins / metabolism Hydrogen Peroxide / metabolism Mitogen-Activated Protein Kinases / metabolism Myocardium / metabolism Oxidative Stress Protein Structure, Tertiary Rats Rats, Sprague-Dawley Reactive Oxygen Species / metabolism* Virulence Factors, Bordetella / pharmacology beta-Adrenergic Receptor Kinases
IF 42.779
Times Cited 207
DNA material AxCALacZ Adex1CAlacZ (RDB02726)