期刊
NEUROBIOLOGY OF DISEASE
卷 17, 期 1, 页码 99-107出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.nbd.2004.06.001
关键词
acidic sphingomyelinase; Alzheimer's disease; cerebral amyloid angiopathy; blood-brain barrier; ceramide; sphingomyelinase; oxidative stress; reactive oxygen species
资金
- NINDS NIH HHS [NS41525] Funding Source: Medline
We have explored the molecular mechanism underlying amyloid betapeptide (Abeta)-mediated cytotoxicity in vitro. Exposure of marine cerebral endothelial cells (CECs) or C6 glioma cells to Abeta25-35 resulted in dose-dependent cell death. Ceramide is a pro-apoptotic lipid mediator. Forced elevation of cellular ceramide levels, either by application of an exogenous C2 ceramide analogue or bacterial sphingomyelinase that induces endogenous ceramide release from sphingomyelin, mimicked Abeta25-35 cytotoxicity in both CECs and C6 glioma cells. Abeta25-35-induced synthesis of ceramide was selectively mediated by activation of neutral sphingomyelinase (nSMase), but not acidic sphingomyelinase (aSMase) or ceramide synthase. Both 3-O-Me-SM and N-acetyl-L-cysteine, the selective and nonselective pharmacological inhibitors of nSMase, respectively, suppressed nSMase activation, ceramide production, and cytotoxic action induced by Abeta25-35 in CECs. Furthermore, genetic knockdown of nSMase by an antisense strategy rendered C6 glioma cells specifically resistant to Abeta25-35 cytotoxicity without affecting their vulnerability to serum deprivation. Together, nSMase activation with subsequent ceramide production may contribute, at least partially, to Abeta25-35 cytotoxicity in cell types with cerebral endothelial and glial lineage. (C) 2004 Elsevier Inc. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据