| 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
|
|
WOS Category
|
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
| Resource |
| DNA material |
AxCALacZ Adex1CAlacZ (RDB02726) |
