Rac1 relieves neuronal injury induced by oxygenglucose deprivation and re-oxygenation via regulation of mitochondrial biogenesis and function.
Rac1 relieves neuronal injury induced by oxygenglucose deprivation and re-oxygenation via regulation of mitochondrial biogenesis and function.
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Rac1 通过调节线粒体生物发生和功能减轻氧葡萄糖剥夺和复氧引起的神经元损伤
DOI：
10.4103/1673-5374.280325
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发表时间：
2020-10
影响因子：
6.1
通讯作者：
Ye Z
中科院分区：
文献类型：
--
作者：
Xia PP;Zhang F;Chen C;Wang ZH;Wang N;Li LY;Guo QL;Ye Z
某些microRNAs（miRNAs）可在再灌注/缺血脑损伤后作为神经保护因子发挥作用。miRNA-142- 3 p可以通过负调节Rac 1的活性参与肿瘤的发生发展和心肌缺血损伤，但目前尚不清楚miRNA-142- 3 p是否也参与脑缺血/再灌注损伤。在本研究中，建立了原代皮层神经元的氧-葡萄糖剥夺/再给氧模型，并用miR-142- 3 p agomir或miR-142- 3 p agomir转染神经元。当暴露于氧-葡萄糖剥夺/再给氧时，miR-142- 3 p在神经元中的表达下调。miR-142- 3 p过表达可显著促进缺氧/复氧诱导的细胞死亡和凋亡，改善线粒体生物合成和功能，包括过氧化物酶体增殖物激活受体γ共激活因子1α、线粒体转录因子A和核呼吸因子1的表达。然而，如果miR-142- 3 p被抑制，则产生相反的效果。荧光素酶报告基因检测证实Rac家族小GTd 1（Rac 1）是miR-142- 3 p的靶基因。过表达的miR-142- 3 p抑制NOX 2活性和Rac 1和Rac 1-GT3（其活化形式）的表达。miR-142- 3 p抑制剂在氧-葡萄糖剥夺/再氧合后具有相反的作用。我们的研究结果表明，miR-142- 3 p下调Rac 1的表达和激活，调节线粒体生物发生和功能，抑制氧糖剥夺损伤，从而发挥神经保护作用。实验于2017年3月7日获得中南大学实验动物使用与管理委员会批准（批准号：201703346）。
Certain microRNAs (miRNAs) can function as neuroprotective factors after reperfusion/ischemia brain injury. miRNA-142-3p can participate in the occurrence and development of tumors and myocardial ischemic injury by negatively regulating the activity of Rac1, but it remains unclear whether miRNA-142-3p also participates in cerebral ischemia/reperfusion injury. In this study, a model of oxygen-glucose deprivation/re-oxygenation in primary cortical neurons was established and the neurons were transfected with miR-142-3p agomirs or miR-142-3p antagomirs. miR-142-3p expression was down-regulated in neurons when exposed to oxygen-glucose deprivation/re-oxygenation. Over-expression of miR-142-3p using its agomir remarkably promoted cell death and apoptosis induced by oxygen-glucose deprivation/re-oxygenation and improved mitochondrial biogenesis and function, including the expression of peroxisome proliferator-activated receptor-γ coactivator-1α, mitochondrial transcription factor A, and nuclear respiratory factor 1. However, the opposite effects were produced if miR-142-3p was inhibited. Luciferase reporter assays verified that Rac Family Small GTPase 1 (Rac1) was a target gene of miR-142-3p. Over-expressed miR-142-3p inhibited NOX2 activity and expression of Rac1 and Rac1-GTPase (its activated form). miR-142-3p antagomirs had opposite effects after oxygen-glucose deprivation/re-oxygenation. Our results indicate that miR-142-3p down-regulates the expression and activation of Rac1, regulates mitochondrial biogenesis and function, and inhibits oxygen-glucose deprivation damage, thus exerting a neuroprotective effect. The experiments were approved by the Committee of Experimental Animal Use and Care of Central South University, China (approval No. 201703346) on March 7, 2017.