The Role of SUMO-Conjugating Enzyme Ubc9 in the Neuroprotection of Isoflurane Preconditioning Against Ischemic Neuronal Injury
The Role of SUMO-Conjugating Enzyme Ubc9 in the Neuroprotection of Isoflurane Preconditioning Against Ischemic Neuronal Injury
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SUMO 结合酶 Ubc9 在异氟烷预处理对缺血性神经元损伤的神经保护中的作用
DOI：
10.1007/s12035-014-8797-3
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发表时间：
2015-06-01
影响因子：
5.1
通讯作者：
Xiong, Lize
中科院分区：
文献类型：
--
作者：
Tong, Li;Wu, Zhixin;Xiong, Lize
用挥发性麻醉剂进行预适应可产生抗脑缺血再灌注损伤的缺血耐受性。我们研究了泛素结合酶9(Ubc9)是否与异氟烷预适应(IsoPC)诱导的神经保护有关。体外检测复氧后4h和2 4h Ubc9蛋白的表达。在存在或不存在Ubc9小干扰RNA(SiRNA)的情况下，评估Ubc9在神经保护作用中的作用。在体内，大鼠预先暴露1h~2%异氟醚，连续5d，然后阻断大脑中动脉。分别于再灌注后不同时间测定神经行为评分和脑梗塞体积。采用侧脑室微量注射Ubc9 siRNA的方法评价Ubc9在缺血耐受中的作用。结果表明，异氟醚预适应可提高缺氧缺糖条件下SH-SY5Y细胞的存活率。它还缩小了脑梗塞体积，改善了局灶性脑缺血大鼠的神经学结果。异氟醚预适应可上调Ubc9的表达。Ubc9基因敲除可显著减弱异氟醚预适应诱导的神经保护作用。异氟醚预适应诱导的神经保护作用是通过Ubc9介导的。这些结果提示异氟醚预适应诱导脑缺血耐受的新机制。
Preconditioning with volatile anesthetics can create an ischemia tolerance against cerebral ischemia-reperfusion injury. We investigated whether ubiquitin conjugase 9 (Ubc9), the E2 conjugase for SUMOylation, is associated with neuroprotection induced by isoflurane preconditioning (IsoPC). In vitro, Ubc9 protein expression was evaluated at 4 and 24 h after reoxygenation. The role of Ubc9 in the neuroprotective effect was assessed in the presence or absence of Ubc9 small interfering RNA (siRNA). In vivo, rats were preconditionally exposed for 1 h to 2 % isoflurane for five consecutive days followed by middle cerebral artery occlusion. Neurobehavioral scores and infarction volume were determined at different times after reperfusion. The role of Ubc9 in ischemic tolerance was evaluated by intracerebroventricular microinjection with the Ubc9 siRNA. We showed that isoflurane preconditioning improved the cell viability of the SH-SY5Y cells that were challenged by oxygen-glucose deprivation. It also reduced brain infarct volumes and improved neurologic outcomes in the focal cerebral ischemic rat. The expression of Ubc9 was upregulated by isoflurane preconditioning. Knockdown of Ubc9 significantly attenuated the isoflurane preconditioning-induced neuroprotective effects. Isoflurane preconditioning-induced neuroprotection against ischemic injuries is mediated by Ubc9. These results suggest a novel mechanism for isoflurane preconditioning-induced tolerance to cerebral ischemia.