Corticotropin-releasing hormone induces Fas ligand production and apoptosis in PC12 cells via activation of p38 mitogen-activated protein kinase
Corticotropin-releasing hormone induces Fas ligand production and apoptosis in PC12 cells via activation of p38 mitogen-activated protein kinase
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DOI：
10.1074/jbc.m111236200
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发表时间：
2002-04-05
影响因子：
4.8
通讯作者：
Margioris, AN
中科院分区：
文献类型：
--
作者：
Dermitzaki, E;Tsatsanis, C;Margioris, AN
最近的实验结果涉及促肾上腺皮质激素释放激素（CRH）的细胞反应伤害性刺激和可能的凋亡。本工作的目的是研究CRH对细胞凋亡和Fas/Fas配体系统的影响在体外模型中，PC 12大鼠嗜铬细胞瘤细胞系，这是广泛用于细胞凋亡的研究，并在同一时间表达CRH/CRH受体系统。我们发现了以下情况。CRH诱导Fas配体产生和细胞凋亡。这些作用是由CRH I型受体介导的，因为其拮抗剂antalarmin阻断了CRH诱导的细胞凋亡和Fas配体表达。CRH激活p38丝裂原活化蛋白激酶，这被认为是必不可少的CRH诱导的细胞凋亡和Fas配体的生产。CRH还促进了ERK 1/2的快速和短暂的激活，然而，这对于CRH诱导的细胞凋亡或Fas配体的产生是不必要的。因此，CRH通过CRH I型受体促进PC 12细胞凋亡，CRH I型受体通过激活p38诱导Fas配体产生。
Recent experimental findings involve corticotropin-releasing hormone (CRH) in the cellular response to noxious stimuli and possibly apoptosis. The aim of the present work was to examine the effect of CRH on apoptosis and the Fas/Fas ligand system in an in vitro model, the PC12 rat pheochromocytoma cell line, which is widely used in the study of apoptosis and at the same time expresses the CRH/CRH receptor system. We have found the following. CRH induced Fas ligand production and apoptosis. These effects were mediated by the CRH type I receptor because its antagonist antalarmin blocked CRH-induced apoptosis and Fas ligand expression. CRH activated p38 mitogen-activated protein kinase, which was found to be essential for CRH-induced apoptosis and Fas ligand production. CRH also promoted a rapid and transient activation of ERK1/2, which, however, was not necessary for either CRH-induced apoptosis or Fas ligand production. Thus, CRH promotes PC12 apoptosis via the CRH type I receptor, which induces Fas ligand production via activation of p38.