Autophagic effect of programmed cell death 5 (PDCD5) after focal cerebral ischemic reperfusion injury in rats
Autophagic effect of programmed cell death 5 (PDCD5) after focal cerebral ischemic reperfusion injury in rats
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DOI：
10.1016/j.neulet.2014.02.066
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发表时间：
2014-04-30
影响因子：
2.5
通讯作者：
Zhou, Chang-Man
中科院分区：
文献类型：
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作者：
Jiang, Zhao;Chen, Chun-Hua;Zhou, Chang-Man
以往的研究表明，程序性细胞死亡5（programmed cell death 5，PDCD 5）蛋白可通过内源性或外源性途径加速多种细胞对刺激的应答性凋亡过程。本研究旨在首次证实大鼠局灶性脑缺血损伤后PDCD 5蛋白水平与自噬活性相关。将125只Sprague-Dawley大鼠（雄性）随机分为以下组：假手术组、大脑中动脉闭塞/再灌注（MCAO）组、MCAO +对照siRNA组和MCAO + PDCD 5 siRNA组。结果测量包括神经行为结果、脑梗死体积、脑含水量、BBB破坏、MRI和双荧光标记。Western blot和组织病理学方法检测PDCD 5和Beclin 1等促自噬蛋白的表达及LC 3-II/LC 3-I比值。研究发现，通过侧脑室注射PDCD 5 siRNA降低PDCD 5表达显著改善神经行为结果，降低梗死率，脑水肿和BBB破坏。这些结果与半暗带区Beclin 1表达和LC 3-II/LC 3-I比值降低相关。自噬诱导剂雷帕霉素部分减弱了PDCD 5 siRNA的作用。总之，这项研究表明，PDCD 5是自噬的关键调节因子，可能在MCAO损伤后发挥重要作用。(C)2014爱思唯尔爱尔兰有限公司版权所有。
Former studies indicated that programmed cell death 5 (PDCD5) protein could accelerate the process of apoptosis in response to some stimuli in various kinds of cells via the intrinsic or extrinsic pathway. In this study, we aimed to demonstrate for the first time that protein level of PDCD5 are related to autophagic activity after focal ischemic brain injury in rats. One hundred and twenty-five Sprague-Dawley rats (male) were randomly divided into the following groups: Sham operated, Middle Cerebral Artery Occlusion/Reperfusion (MCAO), MCAO + Control siRNA and MCAO + PDCD5 siRNA. Outcome measurements include neurobehavioral outcomes, brain infarct volume, brain water content, BBB disruption, MRI and double fluorescence labeling. Western blot and histopathophysiological techniques were used to measure the expression of PDCD5 and some pro-autophagic proteins such as Beclin 1 and the LC3-II/LC3-I ratio. The study found that decreased PDCD5 expression via intracerebroventricular injection of PDCD5 siRNA significantly improved the neurobehavioral outcome, reduced the infarct ratio, cerebral edema and BBB disruption. These results were associated with decreased expression of Beclin 1 and the LC3-II/LC3-I ratio in the penumbra area. Rapamycin, an inducer of autophagy, partially weakened the effect of PDCD5 siRNA. In conclusion, this study suggested that PDCD5 was a key regulator of autophagy that might play an important role following MCAO injury. (C) 2014 Elsevier Ireland Ltd. All rights reserved.