ROLE OF PROTEIN-KINASE-C IN OXIDANT - MEDIATED ACTIVATION OF PHOSPHOLIPASE-A(2) IN RABBIT PULMONARY ARTERIAL SMOOTH-MUSCLE CELLS

The present study was undertaken to test the hypothesis that activatio n of cell membrane associated protein kinase C (PKC) plays a role in s timulating cell membrane associated phospholipase A2 (PLA2) activity, and subsequent liberation of arachidonic acid (AA) under exposure of r abbit pulmonary arterial smooth muscle cells to the oxidant hydrogen p eroxide (H2O2). Exposure of the smooth muscle cells to H2O2 dose-depen dently stimulates [C-14] AA release, and enhances the cell membrane as sociated PLA2 activity. Pretreatment of the cells with protein kinase C (PKC) inhibitors H7 and sphingosine prevent the cell membrane associ ated PLA2 activity, and AA release caused by H2O2. Treatment of the sm ooth muscle cells with H2O2 stimulates the cell membrane associated PK C activity Pretreatment of the cells with an antioxidant vitamin E pre vents H2O2 caused stimulation of the cell membrane associated PKC acti vity. The cell membrane associated PLA2 and PKC activities correlate l inearly. These results suggest that H2O2 caused stimulation of the smo oth muscle cell membrane associated PLA2 activity, and subsequent libe ration of AA can occur through an increase in the activity of the cell membrane associated PKC.