Redox regulation of signal transduction in smooth muscle cells: distinct effects of PKC-down regulation and PKC inhibitors on oxidant induced MAP kinase.

Reactive oxygen species function as signaling molecules, and are known to be generated under both normal and pathological conditions. Using vascular smooth muscle cells, we have demonstrated an increase in mitogen activated protein kinase activity in response to oxidants. Mitogen activated protein kinase activity increased linearly with time in cells treated with pervanadate. Hydrogen peroxide also caused rapid induction of mitogen activated protein kinase. Protein kinase C down regulation partially decreased induction of mitogen activated protein kinase activity by oxidants, and the Ca2+ ionophore, ionomycin. Protein kinase C inhibitors, compound-3 and bisindolylmaleimide did not inhibit oxidant induced mitogen activated protein kinase activity, where as calphostin C activated it. The tyrosine kinase inhibitors genistein, herbimycin A and tyrphostin caused 50% inhibition of oxidant induced mitogen activated protein kinase activation. These results suggest that oxidant-induced mitogen activated protein kinase is protein kinase C independent.