Increased cerebral protein ISGylation after focal ischemia is neuroprotective
Increased cerebral protein ISGylation after focal ischemia is neuroprotective
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DOI：
10.1038/jcbfm.2011.103
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发表时间：
2011-12-01
影响因子：
6.3
通讯作者：
Vemuganti, Raghu
中科院分区：
文献类型：
--
作者：
Nakka, Venkata P.;Lang, Bradley T.;Vemuganti, Raghu
添加名为 ISG15 的小肽称为 ISGylation，它是一种泛素 (ub) 样翻译后修饰。我们目前表明，成年小鼠短暂大脑中动脉闭塞（MCAO）引起的局灶性缺血可在再灌注 6 至 24 小时之间显着诱导皮质蛋白 ISGylation。通过二维蛋白质印迹，观察到与假手术对照相比，局灶性缺血后 45 种蛋白质的 ISGylation 显着增加（1.8 至 9.7 倍）。免疫化学显示，ISG 化蛋白定位于缺血小鼠同侧纹状体内的神经元和梗死周围皮质内的星形胶质细胞中。当进行短暂的MCAO时，与野生型对照相比，ISG15(-/-)小鼠表现出死亡率增加、梗塞加剧和神经系统恢复恶化。此外，缺乏UBE1L（ub激活酶E1样蛋白，ISG化周期的第一个酶）的小鼠在接受短暂的MCAO时也表现出更大的梗塞。与野生型对照相比，两种基因敲除的区域脑血流或其他生理参数没有显着差异。这些研究表明，增加的蛋白质 ISGylation 可能是一种内源性神经保护适应，可最大限度地减少中风后脑损伤。脑血流与代谢杂志 (2011) 31, 2375-2384; doi：10.1038/jcbfm.2011.103； 2011 年 8 月 17 日在线发布
Addition of a small peptide called ISG15 is known as ISGylation, which is an ubiquitin (ub)-like posttranslational modification. We currently show that focal ischemia induced by transient middle cerebral artery occlusion (MCAO) in adult mice significantly induces cortical protein ISGylation between 6 and 24 hours reperfusion. With two-dimensional western blotting, 45 proteins were observed to be significantly increased in ISGylation (by 1.8- to 9.7-fold) after focal ischemia compared with sham control. Immunochemistry showed that ISGylated proteins are localized in neurons within the ipsilateral striatum and in astroglia within the peri-infarct cortex of ischemic mice. When subjected to transient MCAO, ISG15(-/-) mice showed increased mortality, exacerbated infarction, and worsened neurologic recovery than did wild-type controls. In addition, mice lacking UBE1L (ub-activating enzyme E1-like protein, the first enzyme of the ISGylation cycle) also showed bigger infarcts when subjected to transient MCAO. Regional cerebral blood flow or other physiologic parameters were not significantly different in both knockouts compared with wild-type controls. These studies indicate that increased protein ISGylation might be an endogenous neuroprotective adaptation to minimize poststroke brain damage. Journal of Cerebral Blood Flow & Metabolism (2011) 31, 2375-2384; doi:10.1038/jcbfm.2011.103; published online 17 August 2011