Rac1 relieves neuronal injury induced by oxygenglucose deprivation and re-oxygenation via regulation of mitochondrial biogenesis and function

• Main Authors: Ping-Ping Xia, Fan Zhang, Cheng Chen, Zhi-Hua Wang, Na Wang, Long-Yan Li, Qu-Lian Guo, Zhi Ye
• Format: Article
• Language: English
• Published: Wolters Kluwer Medknow Publications 2020-01-01
• Series: Neural Regeneration Research
• Subjects: biogenesis; ischemia/reperfusion injury; micrornas; mir-142-3p; mitochondria; neuroprotection; nox2; oxygen-glucose deprivation; rac1
• Online Access: http://www.nrronline.org/article.asp?issn=1673-5374;year=2020;volume=15;issue=10;spage=1937;epage=1946;aulast=

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.