Protective and Antioxidative Effects of GM1 Ganglioside in PC12 Cells Exposed to Hydrogen Peroxide are Mediated by Trk Tyrosine Kinase

GM1 ganglioside was found to increase the survival of PC12 cells exposed to H2O2, its action was blocked by Trk tyrosine kinase inhibitor K-252a. Thus, the inhibition of H2O2 cytotoxic action by GM1 constituted 52.8 +/- A 4.3%, but in the presence of 1.0 mu M K-252a it was only 11.7 +/- A 10.8%, i.e. the effect of GM1 became insignificant. Exposure to GM1 markedly reduced the increased accumulation of reactive oxygen species (ROS) and diminished the inactivation of Na+,K+-ATPase induced in PC12 cells by H2O2, but in the presence of K-252a GM1 did not change these metabolic parameters. The inhibitors of extracellular signal-regulated protein kinase, phosphatidyl inositol 3-kinase and protein kinase C decreased the effects of GM1. A combination of these protein kinase inhibitors reduced inhibition of H2O2 cytotoxic action by GM1 to the larger extent than each of the inhibitors and practically abolished the ability of GM1 to decrease H2O2-induced ROS accumulation. The protective and antioxidative effects of GM1 in PC12 cells exposed to H2O2 appear to be mediated by activation of Trk receptor tyrosine kinase and the protein kinases downstream from this enzyme.