Ceramide is involved in MPP<SUP>&#8290;</SUP>-induced Cytotoxicity in Human Neuroblastoma Cells

Ceramide is involved in MPP<SUP>&#8290;</SUP>-induced Cytotoxicity in Human Neuroblastoma Cells

<P> To understand the cytotoxic mechanism of MPP<SUP>&#8290;</SUP>, we examined the involvement of ceramide in MPP<SUP>&#8290;</SUP>- induced cytotoxicity to human neuroblastoma SH-SY5Y cells. When SH-SY5Y cells were exposed to MPP<SUP>&#8290;</SUP>, MPP<SUP>&#8290;</SUP> induced dose-dependent cytotoxicity accompanied by 2-fold elevation of intracellular ceramide levels in SH-SY5Y cells. Three methods were used to test the hypothesis that the elevated intracellular ceramide is related to MPP<SUP>&#8290;</SUP>-induced cytotoxicity: C<SUB>2</SUB>-ceramide was directly applied to cells, sphingomyelinase (SMase) was exogenously added, and oleoylethanolamine (OE) was used to inhibit degradation of ceramide. Furthermore, inhibition of ceramide-activated protein phosphatase (CAPP), the effector of ceramide, using okadaic acid (OA) attenuated cell death but treatment of fumonisin B<SUB>1</SUB>, the ceramide synthase inhibitor, did not alter the cytotoxic effect of MPP<SUP>&#8290;</SUP>. Based on these, we suggest that the elevation of intracellular ceramide is one of the important mediators in MPP<SUP>&#8290;</SUP>- induced cell death.