Up-Regulation of Glis2 Involves in Neuronal Apoptosis After Intracerebral Hemorrhage in Adult Rats

Up-Regulation of Glis2 Involves in Neuronal Apoptosis After Intracerebral Hemorrhage in Adult Rats
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DOI:
10.1007/s10571-014-0130-1
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发表时间:
2015-04-01
影响因子:
4
通讯作者:
Cao, Maohong
Cao, Maohong
中科院分区:
医学3区
文献类型:
--
作者:
Ke, Kaifu;Song, Yan;Cao, Maohong

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新发现的Kruppel样锌指蛋白Gli-similar 2(Glis2)是转录因子中的一员,参与控制遗传信息流和多种细胞活动的调节。越来越多的证据表明,它在成人发育和几种疾病中发挥着重要作用。然而,关于Glis2在中枢神经系统中的调节和可能的功能的信息仍然有限。在本研究中,我们探讨了Glis2在脑出血(ICH)病理生理过程中的作用。建立大鼠脑出血模型,并进行行为学评价。脑出血后血肿周围脑区Glis2表达显著上调。免疫荧光显示,Glis2在神经元中显著增加,但不包括星形胶质细胞或小胶质细胞。在体内和体外研究中发现,Glis2的上调伴随着caspase-3和Bax活性的表达增加,而Bcl2的表达降低。此外,通过RNA干扰下调PC12细胞中Glis2的表达,降低了caspase-3和Bax的活性,而增加了Bcl-2的表达。综上所述,我们推测Glis2可能在脑出血后的神经元中发挥促凋亡作用。
The novel Kruppel-like zinc finger protein Gli-similar 2 (Glis2), one member of the transcription factors, is involved in controlling the flow of genetic information and the modulation of diverse cellular activities. Accumulating evidence has demonstrated its important roles in adult development and several diseases. However, information regarding the regulation and possible function of Glis2 in the central nervous system is still limited. In this study, we explored the roles of Glis2 during the pathophysiological process of intracerebral hemorrhage (ICH). An ICH rat model was established and assessed by behavioral tests. Expression of Glis2 was significantly up-regulated in brain areas surrounding the hematoma following ICH. Immunofluorescence showed that Glis2 was strikingly increased in neurons, but not astrocytes or microglia. Up-regulation of Glis2 was found to be accompanied by the increased expression of active caspase-3 and Bax and decreased expression of Bcl-2 in vivo and vitro studies. Moreover, knocking down Glis2 by RNA-interference in PC12 cells reduced active caspase-3 and Bax expression while increased Bcl-2. Collectively, we speculated that Glis2 might exert pro-apoptotic function in neurons following ICH.