Redox regulation of signal transduction in smooth muscle cells: protein kinase C inhibition by thiol agents.
Thiol depleting agents phenylarsine oxide and N-ethylmaleimide significantly inhibited the phorbol ester induced protein kinase C activation in vascular smooth muscle cells. Phenylarsine oxide is a good protein tyrosine phosphatase inhibitor. Sodium orthovanadate, also a protein tyrosine phosphatase inhibitor, neither activated nor inhibited protein kinase C in vascular smooth muscle cells. Phenylarsine oxide, N-ethylmaleimide, orthovanadate, hydrogen peroxide and pervanadate [sodium orthovanadate + hydrogen peroxide] all significantly induced mitogen activated protein kinase in vascular smooth muscle cells. Phorbol ester and platelet derived growth factor induced mitogen activated protein kinase was inhibited by phenylarsine oxide pretreatment to vascular smooth muscle cells. However, hydrogen peroxide/pervanadate induced mitogen activated protein kinase was not prevented by phenylarsine oxide. These results suggest that oxidation of the cellular thiols inhibits the protein kinase C and activates mitogen activated protein kinase in vascular smooth muscle cells. In addition, peroxides induced, the activation of mitogen activated protein kinase in vascular smooth muscle cells which is independent of protein kinase C.
Taher
M M
MM
Department of Surgery, Medical College of Virginia, Richmond 23298, USA. MTAHER@GEMS.VCU.EDU
Abd-Elfattah
A S
AS
D001152:Arsenicals / Q000494:pharmacology*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D005033:Ethylmaleimide / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D010084:Oxidation-Reduction; D010766:Phosphorylation; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D015398:Signal Transduction; D014638:Vanadates / Q000494:pharmacology
D001152:Arsenicals; D010975:Platelet Aggregation Inhibitors; C029341:oxophenylarsine; D014638:Vanadates; D006861:Hydrogen Peroxide; D011493:Protein Kinase C; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D005033:Ethylmaleimide