Attenuation of cortical neuronal apoptosis by gangliosides

Addition of the natural gangliosides monosialoganglioside (GM1), disialogan glioside, trisialoganglioside, or tetrasialoganglioside in the range of 10 to 100 mu M, but not asialoganglioside lacking the sialic acid moiety, atte nuated cortical neuronal apoptosis induced by serum deprivation, ionomycin, or cyclosporin A but not by protein kinase inhibitors (staurosporine, geni stein, lavendustin A, or herbimycin A). Coaddition of 100 nM wortmannin, a selective inhibitor of phosphatidylinositol 3-kinase, but not 1 mu M Go6976 , a selective protein kinase C inhibitor, blocked the neuroprotective effec t of GM1. In contrast to its antiapoptotic effect, GM1 at up to 200 mu M di d not attenuate cortical neuronal necrosis induced by exposure to the excit otoxins N-methyl-o-aspartate or kainate. Furthermore, GM1 increased the nec rosis induced by oxidative stress (addition of Fe2+ or buthionine sulfoximi ne). These data suggest that neuroprotective effects of natural ganglioside s may preferentially reflect reduction of neuronal apoptosis rather than ne crosis, and be mediated through mechanisms involving activation of phosphat idylinositol 3-kinase.