文章基本信息

标题：Heterogeneity in the sn-1 carbon chain of platelet-activating factor glycerophospholipids determines pro- or anti-apoptotic signaling in primary neurons
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作者：Scott D. Ryan ; Cory S. Harris ; Casey L. Carswell 等
期刊名称：JLR Papers In Press
印刷版ISSN：0022-2275
电子版ISSN：1539-7262
出版年度：2008
卷号：49
期号：10
页码：2250-2258
DOI：10.1194/jlr.M800263-JLR200
语种：English
出版社：American Society for Biochemistry and Molecular Biology
摘要：The platelet-activating factor (PAF) family of glycerophospholipids accumulates in damaged brain tissue following injury. Little is known about the role of individual isoforms in regulating neuronal survival. Here, we compared the neurotoxic and neuroprotective activities of 1- O -hexadecyl-2-acetyl- sn -glycero-3-phosphocholine (C₁₆-PAF) and 1- O -octadecyl-2-acetyl- sn -glycero-3-phosphocholine (C₁₈-PAF) in cerebellar granule neurons. We find that both C₁₆-PAF and C₁₈-PAF cause PAF receptor-independent death but signal through different pathways. C₁₆-PAF activates caspase-7, whereas C₁₈-PAF triggers caspase-independent death in PAF receptor-deficient neurons. We further show that PAF receptor signaling is either pro- or anti-apoptotic, depending upon the identity of the sn -1 fatty acid of the PAF ligand. Activation of the PAF G-protein-coupled receptor (PAFR) by C₁₆-PAF stimulation is anti-apoptotic and inhibits caspase-dependent death. Activation of PAFR by C₁₈-PAF is pro-apoptotic. These results demonstrate the importance of the long-chain sn -1 fatty acid in regulating PAF-induced caspase-dependent apoptosis, caspase-independent neurodegeneration, and neuroprotection in the presence or absence of the PAF receptor.