Essential role of Rac GTPase in hydrogen peroxide-induced activation of c-fos serum response element.

In the present study, we investigated whether hydrogen peroxide activates c-fos serum response element (SRE) in Rat-2 fibroblast cells. By transient transfection analysis, exogenous H2O2 stimulated SRE-dependent reporter gene activity in a dose and time-dependent manner. Also, we examined the role of Rac GTPase and phospholipase A2 (PLA2) in the H2O2-induced SRE activation. Either transfection of a dominant negative Rac mutant, RacN17, plasmid or pretreatment of mepacrine, a potent inhibitor of PLA2, blocked H2O2-induced SRE activation dramatically. Together, these findings suggest a critical role of 'Rac and subsequent activation of phospholipase A2' in the signaling pathway of H2O2 to SRE.