RT Journal Article SR Electronic T1 Attenuation of Cortical Neuronal Apoptosis by Gangliosides JF Journal of Pharmacology and Experimental Therapeutics JO J Pharmacol Exp Ther FD American Society for Pharmacology and Experimental Therapeutics SP 811 OP 816 VO 290 IS 2 A1 Bo Rum Ryu A1 Dennis W. Choi A1 Dean M. Hartley A1 Erminio Costa A1 Ilo Jou A1 Byoung Joo Gwag YR 1999 UL http://jpet.aspetjournals.org/content/290/2/811.abstract AB Addition of the natural gangliosides monosialoganglioside (GM1), disialoganglioside, trisialoganglioside, or tetrasialoganglioside in the range of 10 to 100 μM, but not asialoganglioside lacking the sialic acid moiety, attenuated cortical neuronal apoptosis induced by serum deprivation, ionomycin, or cyclosporin A but not by protein kinase inhibitors (staurosporine, genistein, lavendustin A, or herbimycin A). Coaddition of 100 nM wortmannin, a selective inhibitor of phosphatidylinositol 3-kinase, but not 1 μM Go6976, a selective protein kinase C inhibitor, blocked the neuroprotective effect of GM1. In contrast to its antiapoptotic effect, GM1 at up to 200 μM did not attenuate cortical neuronal necrosis induced by exposure to the excitotoxins N-methyl-d-aspartate or kainate. Furthermore, GM1 increased the necrosis induced by oxidative stress (addition of Fe2+ or buthionine sulfoximine). These data suggest that neuroprotective effects of natural gangliosides may preferentially reflect reduction of neuronal apoptosis rather than necrosis, and be mediated through mechanisms involving activation of phosphatidylinositol 3-kinase. The American Society for Pharmacology and Experimental Therapeutics