Involvement of de novo ceramide biosynthesis in lymphotoxin-induced oligodendrocyte death

被引:21
作者
Plo, I
Ghandour, S
Feutz, AC
Clanet, M
Laurent, G
Bettaieb, A
机构
[1] Inst Claudius Regaud, INSERM, E9910, F-31052 Toulouse, France
[2] Fac Med Strasbourg, Inst Chim Biol, CNRS, UPR 416, Strasbourg, France
[3] CHU Purpan, Serv Neurol, Toulouse, France
[4] Fac Pharm, Serv Hematol, Dijon, France
[5] Fac Pharm, INSERM, U517, Dijon, France
关键词
ceramide; ceramide synthase; death; lymphotoxin; oligodendrocyte;
D O I
10.1097/00001756-199908020-00028
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
BOTH experimental and clinical studies suggest that lymphotoxin (LT) plays an important role in multiple sclerosis (MS) by inducing oligodendrocyte (OL)depletion. However, the mechanism of LT cytotoxicity is unknown. Because of the role of ceramide as a cell death mediator for a large variety of cytotoxic molecules, we have investigated the possible role of this second messenger in LT-induced cytotoxicity on SV40 immortalized new-born mice OL. Human recombinant LT exposure (50 ng/ml) resulted in intracellular ceramide accumulation which peaked at 48 h (similar to 170% increase) and paralleled LT-induced cytotoxicity. Moreover, fumonisin B1, a. potent and specific ceramide synthase inhibitor, not only inhibited ceramide accumulation but also protected OL from LT cytotoxicity. These results suggest that LT-induced ceramide synthase stimulation and subsequent increased intracellular ceramide concentration are implicated in oligodendrocyte death. NeuroReport 10:2373-2376 (C) 1999 Lippincott Williams & Wilkins.
引用
收藏
页码:2373 / 2376
页数:4
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