REDOX REGULATION OF SIGNAL-TRANSDUCTION IN VASCULAR SMOOTH-MUSCLE CELLS - THIOL OXIDIZING-AGENTS INDUCED PHOSPHOLIPASE-D

Decrease in intracellular thiols leads to oxidative stress and thus ma y cause alterations in the activity of redox-sensitive enzymes require d for signal transduction. Here, we report that, N-ethylmaleimide and phenylarsine oxide, which are known to oxidize free thiols as well as protein thiols, induced phosphatidyl ethanol generation in the micromo lar range suggesting activation of phospholipase D in vascular smooth muscle cells. These agents also induced significant phosphatidic acid and diacylglycerol generation without causing protein kinase C activat ion. Phenylarsine oxide and N-ethyl maleimide induced phospholipase D activation is protein kinase C independent as it was not inhibited by compound-3 and bisindolyhmaleimide, potent protein kinase C inhibitors . Tyrosine kinase inhibitor herbimycin A by itself activated PLD, but inhibited the phospholipase D activation by phenylarsine oxide and N-e thylmaleimide. These results suggest that oxidation of the cellular th iols activates phospholipase D independent of protein kinase C.