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Ceramide is involved in MPP<SUP></SUP>-induced Cytotoxicity in Human Neuroblastoma Cells
Eun-Joo Nam,Hye-Sook Lee,Young Jae Lee,Wan-Seok Joo,Sungho Maeng,Hye-In Im,Chan-Woong Park,Yong Sik Kim 대한생리학회-대한약리학회 2002 The Korean Journal of Physiology & Pharmacology Vol.6 No.6
<P> To understand the cytotoxic mechanism of MPP<SUP></SUP>, we examined the involvement of ceramide in MPP<SUP></SUP>- induced cytotoxicity to human neuroblastoma SH-SY5Y cells. When SH-SY5Y cells were exposed to MPP<SUP></SUP>, MPP<SUP></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></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></SUP>. Based on these, we suggest that the elevation of intracellular ceramide is one of the important mediators in MPP<SUP></SUP>- induced cell death.