REQUIREMENT FOR GENERATION OF H2O2 FOR PLATELET-DERIVED GROWTH-FACTORSIGNAL-TRANSDUCTION

Stimulation of rat vascular smooth muscle cells (VSMCs) by platelet-de rived growth factor (PDGF) transiently increased the intracellular con centration of hydrogen peroxide (H2O2). This increase could be blunted by increasing the intracellular concentration of the scavenging enzym e catalase or by the chemical antioxidant N-acetylcysteine. The respon se of VSMCs to PDGF, which includes tyrosine phosphorylation, mitogen- activated protein kinase stimulation, DNA synthesis, and chemotaxis, w as inhibited when the growth factor-stimulated rise in H2O2 concentrat ion was blocked. These results suggest that H2O2 may act as a signal-t ransducing molecule, and they suggest a potential mechanism for the ca rdioprotective effects of antioxidants.