CHMP4B, ESCRT-III associating protein, associated with neuronal apoptosis following intracerebral hemorrhage
CHMP4B, ESCRT-III associating protein, associated with neuronal apoptosis following intracerebral hemorrhage
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DOI：
10.1016/j.brainres.2014.11.043
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发表时间：
2015-02
期刊：
影响因子：
2.9
通讯作者：
Jiabing Shen;Yonghua Liu;Yan Song;Lei Li;C. Duan;Ying Zhou;Kaifu Ke
中科院分区：
文献类型：
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作者：
Jiabing Shen;Yonghua Liu;Yan Song;Lei Li;C. Duan;Ying Zhou;Kaifu Ke
带电多泡体蛋白(CHMP)是一个小螺旋蛋白家族，含有一个N端碱性带电区域和一个较小的C端酸性区域，这两个区域在所有真核生物中都高度保守。CHMP4B是运输所需的内体分选复合体(ESCRT)-III的核心成分，是内体分选和其他生物过程所必需的。在这里，我们证明CHMP4B可能参与了脑出血(ICH)过程中的神经细胞凋亡。免疫印迹、免疫组织化学和免疫荧光结果显示，脑出血后血肿周围神经元CHMP4B表达明显上调。CHMP4B水平的升高伴随着Fas受体(Fas)、Fas配体(FasL)、活性caspase-8和活性caspase-3的上调。此外，CHMP4B与Fas和活化的caspase-3在神经元中有很好的共定位，提示其在神经元凋亡中具有潜在的作用。׳S更进一步利用CHMP4BRNA干扰PC12细胞的体外研究，进一步证实CHMP4B可能通过外源性途径在神经细胞凋亡中发挥促凋亡作用。因此，CHMP4B可能在促进脑出血后脑损伤中发挥作用。
Charged multivesicular body protein (CHMP) represents a family of small helical proteins that contain an N-terminal basically charged region and a smaller C-terminal acidic region, which are highly conserved in all eukaryotes. CHMP4B, a core component of the endosomal sorting complex required for transport (ESCRT)-III, is requisite for endosomal sorting and other biological processes. Here, we demonstrate that CHMP4B may be involved in neuronal apoptosis in the processes of intracerebral hemorrhage (ICH). From the results of Western blot, immunohistochemistry and immunofluorescence, we obtained a significant up-regulation of CHMP4B in neurons adjacent to the hematoma following ICH. Increasing CHMP4B level was found to be accompanied by the up-regulation of Fas receptor (Fas), Fas ligand (FasL), active caspase-8, and active caspase-3. Besides, CHMP4B co-localized well with Fas and active caspase-3 in neurons, indicating its potential role in neuronal apoptosis. What׳s more, ourin vitrostudy, using CHMP4B RNA interference in PC12 cells, further confirmed that CHMP4B might exert its pro-apoptotic function on neuronal apoptosis through extrinsic pathway. Thus, CHMP4B may play a role in promoting the brain damage following ICH.