Role of MAPK in ceramide-induced cell death in primary cultured astrocytes from mouse embryonic brain
Role of MAPK in ceramide-induced cell death in primary cultured astrocytes from mouse embryonic brain
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DOI：
10.1016/j.neuro.2005.05.008
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发表时间：
2006-01-01
期刊：
影响因子：
3.4
通讯作者：
Kim, YK
中科院分区：
文献类型：
--
作者：
Oh, HL;Seok, JY;Kim, YK
神经酰胺被认为参与多种细胞信号传导途径，包括促分裂原活化蛋白激酶。本研究旨在探讨神经酰胺诱导的小鼠胚胎脑星形胶质细胞原代培养过程中丝裂原活化蛋白激酶是否参与了神经酰胺诱导的细胞死亡。神经酰胺以剂量和时间依赖性方式诱导细胞凋亡。神经酰胺诱导的细胞死亡依赖于活性氧的产生。神经酰胺引起细胞外信号调节激酶（ERK）和c-Jun N-末端激酶（INK）的激活。这些激酶的药理学抑制剂防止神经酰胺诱导的细胞死亡。神经酰胺诱导Bax表达增加，线粒体膜电位去极化，半胱天冬酶激活。这种作用被ERK和JNK抑制剂抑制。这些结果表明，ERK和JNK的激活参与神经酰胺诱导的星形胶质细胞凋亡，通过一个依赖于神经酰胺的途径。(C)2005年爱思唯尔公司All rights reserved.
Ceramide has been suggested to be involved in a variety of cell signaling pathways including mitogen-activated protein kinases. The present study was undertaken to examine whether mitogen-activated protein kinases are involved in ceramide-induced cell death in primary cultured astrocytes isolated from mouse embryonic brain. Ceramide induced apoptotic death in a dose- and time-dependent manner. Ceramide-induced cell death was dependent on generation of reactive oxygen species. Ceramide caused activation of extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (INK). Pharmacological inhibitors of these kinases prevented ceramide-induced cell death. Ceramide induced an increase in Bax expression, depolarization of mitochondrial membrane potential, and caspase activation. Such effects were inhibited by ERK and JNK inhibitors. These results suggest that activation of ERK and JNK is involved in ceramide-induced apoptosis through a mitochondria-dependent pathway in astrocytes. (C) 2005 Elsevier Inc. All rights reserved.