Phospholipase C-γ1 is required for cell survival in oxidative stress by protein kinase C

Phospholipase C-gamma1 (PLC-gamma1) activation has been reported to enhance cell survival during the cellular response to oxidative stress. We studied the role of protein kinase C (PKC) pathways in mediating PLC-gamma1 survival signalling in oxidative stress by using mouse embryonic fibroblasts genetically deficient in PLC-gamma1 (Plcgl(-/-)) and its wild type (Plcg1(+/+)). PLC-gamma1 was activated by H2O2 treatment in a dose- and time-dependent manner. Activation of PKC was also markedly increased in both cell lines treated with H2O2 (1-5 mM), but with low doses (50-200 muM), PKC activation was considerably decreased in Plcgl(-/-) cells. After treatment with H2O2, PKC-dependent phosphorylation of Bcl-2 and cell viability of Plcgl(-/-) cells decreased dramatically and caspase-3-like activity increased significantly compared with that of the wild-type cells. Furthermore, pretreatment of Plcgl(+/+) cells with PKC-specific inhibitor decreased levels of PKC-dependent Bcl-2 phosphorylation, enhanced caspase-3 activity and their sensitivity to H2O2. On the contrary, treatment of Plcg1(-/-) cells with PKC-specific activator increased the Bcl-2 phosphorylation, decreased caspase-3 activity and improved their survival. These results suggest that PLC-gamma1 mediates survival signalling in oxidative-stress response by PKC-dependent phosphorylation of Bcl-2 and inhibition of caspase-3.