Specific Alterations of the HtrA2/HAX-1 Ratio in the Penumbra Upon Focal Cerebral Ischemia in Mice
Specific Alterations of the HtrA2/HAX-1 Ratio in the Penumbra Upon Focal Cerebral Ischemia in Mice
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DOI：
10.1007/s11064-011-0641-9
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发表时间：
2011-11
影响因子：
4.4
通讯作者：
Abdelhaq Rami;A. Langhagen
中科院分区：
文献类型：
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作者：
Abdelhaq Rami;A. Langhagen
HAX-1是一种线粒体蛋白，在Fas处理、照射或去血清后，在HeLa-和Jurkat细胞中起抗凋亡蛋白的作用。这突显了HAX-1可能参与几种细胞凋亡途径的证据。在此背景下，众所周知，脑缺血所致的细胞死亡涉及受体和线粒体的凋亡机制。本研究采用小鼠局灶性脑缺血模型，主要观察HtrA2、AIF和caspase-3等细胞凋亡剂对Hx-1表达的动态影响。Western印迹和免疫组织化学分析显示，在正常情况下，HAX-1的表达水平很低。局灶性脑缺血后HtrA2表达上调，AIF表达上调，caspase-3激活，HtrA2表达上调，细胞内HAX-1表达明显减少。综上所述，这些结果提示HAX-1可能参与了局灶性脑缺血所致细胞死亡的病理生理过程。
HAX-1 is a mitochondrial protein which acts as an antiapoptotic protein in HeLa- and Jurkat cells after Fas-treatment, irradiation or serum deprivation. This underlines the evidence that HAX-1 might be involved in several apoptotic pathways. In this context, it is known that cell death executed by cerebral ischemia involves both receptor- and mitochondrial apoptotic mechanisms. In this study, we performed focal cerebral ischemia in mice and investigated principally the dynamic changes of HAX-1 expression and other apoptotic agents such as HtrA2, AIF and caspase-3. Western blot and immunohistochemistry analysis revealed that HAX-1 was expressed at very low levels under normal conditions. Focal cerebral ischemia significantly decreased cytosolic accumulation of HAX-1, induced an upregulation of HtrA2, an upregulation of AIF and activation of caspase-3. Taken together, these results suggested that HAX-1 is probably involved in the pathophysiology of cell death induced by focal ischemia.