Estrogen inhibits Fas-mediated apoptosis in experimental stroke.
Estrogen inhibits Fas-mediated apoptosis in experimental stroke.
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DOI：
10.1016/j.expneurol.2008.09.015
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发表时间：
2009-01
影响因子：
5.3
通讯作者：
Xu, Yun
中科院分区：
文献类型：
--
作者：
Jia, Jia;Guan, Dening;Zhu, Wenjing;Alkayed, Nabil J.;Wang, Michael M.;Hua, Zichun;Xu, Yun
雌激素对实验性脑缺血具有保护作用，但其机制尚不清楚。Fas介导的细胞凋亡在脑缺血后被诱导，并在缺血性脑损伤中起重要作用。在这项研究中，我们测试了雌激素是否通过抑制Fas介导的细胞凋亡来保护脑缺血。17只雌性小鼠经β-雌二醇处理和未经处理的卵巢切除（OVX）后，进行大脑中动脉闭塞（MCAO）2 h。分别于再灌注3、6、12 h用RT-PCR和Western blot检测Fas和Fas相关死亡结构域（FADD）的表达。ELISA法检测Fas诱导细胞凋亡的两个下游效应因子caspase-8和caspase-3的活性。最后，Fas抗体诱导的细胞死亡，在原代皮质神经元荧光激活细胞分选仪（FACS）测定的存在和不存在的雌二醇。我们的数据表明，雌激素治疗的OVX雌性小鼠持续较小的梗死相比，未经处理的OVX小鼠。缺血上调Fas和FADD的表达，并增加caspase-8和-3的活性在OVX雌性小鼠皮质，这是显着减弱雌二醇。E2也能显著抑制Fas抗体诱导的神经细胞凋亡。我们的数据表明，抑制缺血诱导的Fas介导的细胞凋亡是雌激素在脑缺血中的神经保护的重要机制。
Estrogen is protective in experimental cerebral ischemia, yet the mechanism remains unclear. Fas-mediated apoptosis has been shown to be induced after cerebral ischemia and significantly contribute to ischemic brain damage. In this study, we tested if estrogen is protective against cerebral ischemia by suppressing Fas-mediated apoptosis. 17β-estradiol-treated and untreated ovariectomized (OVX) female mice were subjected to 2 h middle cerebral artery occlusion (MCAO). Expression of Fas and Fas-associated death domain (FADD) were measured at 3, 6 and 12 h of reperfusion by RT-PCR and Western blot, respectively. Post-ischemic activities of caspase-8 and -3 activities, the two downstream effectors of Fas-induced apoptosis, were also assayed at same time points by ELISA. Finally, Fas antibody-induced cell death in primary cortical neurons was assayed by fluorescence activated cell sorter (FACS) in the presence and absence of estradiol. Our data showed that estradiol-treated OVX female mice sustained smaller infarct compared to untreated OVX mice. Ischemia upregulated Fas and FADD expression, and increased caspase-8 and -3 activities in OVX female mouse cortex, which were significantly attenuated by estradiol. Estradiol also significantly inhibited Fas antibody-induced neuronal cell apoptosis. Our data suggests that inhibition of ischemia-induced Fas-mediated apoptosis is an important mechanism of neuroprotection by estrogen in cerebral ischemia.
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影响因子：
5.3
作者：
Alkayed, NJ;Goto, S;Hurn, PD
通讯作者：
Hurn, PD
DOI：
10.1152/ajpgi.00438.2005
发表时间：
2006-11-01
影响因子：
4.5
作者：
Bharhani, Mantej S.;Borojevic, Rajka;Croitoru, Kenneth
通讯作者：
Croitoru, Kenneth
影响因子：
3.3
作者：
Dimayuga, FO;Reed, JL;Bruce-Keller, AJ
通讯作者：
Bruce-Keller, AJ
影响因子：
6.1
作者：
Saito, Motoko;Yoshigae, Yasushi;Ikeda, Toshihiko
通讯作者：
Ikeda, Toshihiko
影响因子：
4.2
作者：
Xu, Y;Traystman, RJ;Wang, MM
通讯作者：
Wang, MM