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Ceramide is Involved in $MPP^+-induced$ Cytotoxicity in Human Neuroblastoma Cells  

Nam, Eun-Joo (Department of Pharmacology, Seoul National University College of Medicine and Neuroscience Research Institute, Medical Research Center)
Lee, Hye-Sook (Department of Pharmacology, Seoul National University College of Medicine and Neuroscience Research Institute, Medical Research Center)
Lee, Young-Jae (Neuroscience Research Institute, Gachon Medical School)
Joo, Wan-Seok (Department of Pharmacology, Seoul National University College of Medicine and Neuroscience Research Institute, Medical Research Center)
Maeng, Sung-Ho (Department of Pharmacology, Seoul National University College of Medicine and Neuroscience Research Institute, Medical Research Center)
Im, Hye-In (Department of Pharmacology, Seoul National University College of Medicine and Neuroscience Research Institute, Medical Research Center)
Park, Chan-Woong (Department of Pharmacology, Seoul National University College of Medicine and Neuroscience Research Institute, Medical Research Center)
Kim, Yong-Sik (Department of Pharmacology, Seoul National University College of Medicine and Neuroscience Research Institute, Medical Research Center)
Publication Information
The Korean Journal of Physiology and Pharmacology / v.6, no.6, 2002 , pp. 281-286 More about this Journal
Abstract
To understand the cytotoxic mechanism of $MPP^+,$ we examined the involvement of ceramide in $MPP^+-induced$ cytotoxicity to human neuroblastoma SH-SY5Y cells. When SH-SY5Y cells were exposed to $MPP^+,\;MPP^+$ 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 $MPP^+-induced$ cytotoxicity: $C_2-ceramide$ 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 $B_1,$ the ceramide synthase inhibitor, did not alter the cytotoxic effect of $MPP^+.$ Based on these, we suggest that the elevation of intracellular ceramide is one of the important mediators in $MPP^+-induced$ cell death.
Keywords
Dopaminergic neuroblastoma; $MPP^+$; Sphingomyelinase; Ceramide-activated protein phosphatase;
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