Superoxide anion-induced formation of inositol phosphates involves tyrosine kinase activation in smooth muscle cells from rat mesenteric artery

Our previous studies have demonstrated an enhanced production of inositol p hosphates (IPs) induced by superoxide in smooth muscle cells (SMCS). The me chanisms for this effect, however, remained largely unknown. In the present study, it was found that superoxide increased IP production in SMCs from r at mesenteric arteries in a time-dependent manner. The effect of superoxide on IP formation was significantly inhibited by the antioxidants n-acetylcy steine or alpha-lipoic acid. Genistein and tyrphostin A25, two tyrosine kin ase inhibitors, also inhibited the superoxide-induced IP formation. The app lication of monoclonal antibody against phospholipase C-gamma (PLCgamma) si gnificantly inhibited the superoxide-induced IP formation. Finally, the exp ression level of PLC, proteins was increased 6 hrs after exposing SMCs to s uperoxide. The present findings demonstrate that superoxide activates the t yrosine kinase pathway and suggest that the tyrosine kinase-mediated IP for mation may represent a novel mechanism underlying the signalling role of su peroxide in rat mesenteric artery SMCs. (C) 1999 Academic Press.