Estradiol protects PC12 cells against CoCl2-induced apoptosis
Estradiol protects PC12 cells against CoCl2-induced apoptosis
复制标题
DOI：
10.1016/j.brainresbull.2008.04.006
复制
发表时间：
2008-08-15
影响因子：
3.8
通讯作者：
Kim, Won Jae
中科院分区：
文献类型：
--
作者：
Jung, Ji Yeon;Roh, Kwang Hoon;Kim, Won Jae
在缺氧/缺血条件下，神经元发生凋亡事件，导致神经元疾病。雌二醇是一种具有类固醇结构的女性性激素，已知通过中枢神经系统中的多种机制提供神经保护。本研究旨在探讨雌激素抑制氯化钴(CoCl2)诱导的PC12细胞缺氧性死亡的信号转导途径。雌二醇抑制CoCl2诱导的细胞死亡，表现为基因组DNA断裂和形态改变，如细胞皱缩和核浓缩。在CoCl2处理前预先孵育雌二醇会减弱CoCl2介导的ROS的产生，并限制caspase级联反应的活性，如caspase-8、-9和-3。此外，在CoCl2处理的细胞中，雌二醇下调Bax/bcl2的比值，减少细胞色素c从线粒体释放到胞浆中，表明雌二醇影响线粒体的途径。雌二醇还可减弱CoCl2诱导的Fas配体(Fas-L)上调和死亡受体介导的途径中Bid的截断。此外，雌激素通过抑制CoCl2诱导的PC12细胞的ROS生成和通过Bcl2家族、细胞色素c、Fas/Fas-L以及PI3K/Akt途径调节细胞凋亡信号通路，对CoCl2诱导的PC12细胞的凋亡具有神经保护作用。(C)2008 Elsevier Inc.保留所有权利。
In hypoxic/ischemic conditions, neuronal apoptotic events are occurred, resulting in neuronal diseases. Estradiol is a female sex hormone with steroid structure known to provide neuroprotection through multiple mechanisms in the central nervous system. This study was aimed to investigate the signal transduction pathway leading to the inhibitory effects of estradiol against cobalt chloride (CoCl2)-mediated hypoxic death in PC12 cells. Estradiol inhibits CoCl2-induced cell death with genomic DNA fragmentation and morphologic changes such as cell shrinkage and condensed nuclei. Pre-incubation of estradiol prior to CoCl2 treatment attenuated CoCl2-mediated the reactive oxygen species (ROS) production and limited the activities of the caspase cascades, such as caspase-8,-9 and -3. Furthermore, estradiol downregulated the Bax:Bcl-2 ratio and decreased the release of cytochrome c from the mitochondria into the cytosol in CoCl2-treated cells, indicating that estradiol affect on mitochondrial pathway. Estradiol attenuated also CoCl2-induced upregulation of Fas-ligand (Fas-L) and truncated of Bid in sequence of death receptor-mediated pathway. In addition, estradiol increased the phosphorylation of Akt in CoCl2-treated cells, demonstrating that estradiol has no affect on upstream signaling through the PI3K/Akt in inhibition of CoCl2-induced apoptosis in PC12 cells.Taken together, estradiol was found to have a neuroprotective effect against CoCl2-induced apoptosis of PC12 cells by the attenuating ROS production and the modulating apoptotic signal pathway through Bcl-2 family, cytochrome c, Fas/Fas-L as well as PI3K/Akt pathway. (c) 2008 Elsevier Inc. All rights reserved.