Knockout of programmed cell death 5 (PDCD5) gene attenuates neuron injury after middle cerebral artery occlusion in mice
Knockout of programmed cell death 5 (PDCD5) gene attenuates neuron injury after middle cerebral artery occlusion in mice
复制标题
敲除程序性细胞死亡 5 (PDCD5) 基因可减轻小鼠大脑中动脉闭塞后的神经元损伤
DOI：
10.1016/j.brainres.2016.09.005
复制
发表时间：
2016-11-01
期刊：
影响因子：
2.9
通讯作者：
Chen, Chunhua
中科院分区：
文献类型：
--
作者：
Lu, Jianfei;Jiang, Zhao;Chen, Chunhua
von Hippel-Lindau肿瘤抑制蛋白（VHL）的缺失或缺氧导致PDCD 5的核重定位和随后的小鼠双微体2同源物（Mdm 2）降解。因此，VHL可能参与了MCAO后PDCD 5介导的细胞凋亡和自噬。在本研究中，使用PDCD 5敲除（PDCD 5-！-）在小鼠模型上，我们的目的是证明PDCD 5基因敲除可以通过抑制PDCD 5-VHL通路来保护脑免受缺血损伤。MCAO术后24 h，PDCD 5基因敲除小鼠与野生型小鼠相比，脑血流明显改善，神经行为改善，脑梗死减少。凋亡和自噬蛋白的水平在野生型和PDCD 5敲除小鼠中均增加，而它们在野生型小鼠中更明显。我们观察到野生型小鼠MCAO后VHL的表达减少。VHL表达减少可能导致缺氧诱导因子1 α（HIF-1 α）和（BCL 2/腺病毒El B 19 kDa蛋白相互作用蛋白3）BNIP 3表达增加。而PDCD 5缺失小鼠VHL的表达无明显变化，HIF-1 α和BNIP 3的表达略有增加，提示PDCD 5可能通过VHL-HIF-1 α-BNIP 3途径调控细胞凋亡和自噬。(C)© 2016 Elsevier B. V.版权所有。
Loss of von Hippel-Lindau tumor suppressor protein (VHL) or hypoxia results in nuclear relocalization of PDCD5 and subsequent mouse double minute 2 homolog (Mdm2) degradation. Thus, VHL may involved in the PDCD5 mediated apoptosis and autophagy after MCAO. In the present study, using PDCD5 knockout (PDCD5-!-) mice, we aimed to demonstrate that knockout of PDCD5 gene could protect the brain from ischemic injury by inhibiting the PDCD5-VHL pathway. 24 h post MCAO surgery, PDCD5 gene knockout mice presented obvious improved brain blood flow, improved neurological behavior and decreased cerebral infarction compared with wild type mice. The levels of apoptotic and autophagic proteins were increased both in wild type and PDCD5 knockout mice, whereas they were more pronounced in the wild type mice. We observed decrease in the expression of VHL in wild type mice after MCAO. Reduced expression of VHL may result in increased expression of hypoxia-inducible factor 1 alpha(HIF-1 alpha) and (BCL2/adenovirus El B 19 kDa protein-interacting protein 3) BNIP3. However, mice lacking PDCD5 had no changes in the expression of VHL and have slighter increases in the expression of HIF-1 alpha and BNIP3, suggesting that PDCD5 may regulate apoptosis and autophagy through VHL-HIF-1 alpha-BNIP3 pathway. (C) 2016 Elsevier B.V. All rights reserved.