Neuroprotective Effect of miR-483-5p Against Cardiac Arrest-Induced Mitochondrial Dysfunction Mediated Through the TNFSF8/AMPK/JNK Signaling Pathway

Author:

Zhang QiangORCID,Zhan HaohongORCID,Liu CongORCID,Zhang ChenyuORCID,Wei HongyanORCID,Li BoORCID,Zhou DawangORCID,Lu YuanzhengORCID,Huang ShaominORCID,Cheng JinggeORCID,Li ShuhaoORCID,Wang ChuyueORCID,Hu ChunlinORCID,Liao XiaoxingORCID

Abstract

AbstractSubstantial morbidity and mortality are associated with postcardiac arrest brain injury (PCABI). MicroRNAs(miRNAs) are essential regulators of neuronal metabolism processes and have been shown to contribute to alleviated neurological injury after cardiac arrest. In this study, we identified miRNAs related to the prognosis of patients with neurological dysfunction after cardiopulmonary resuscitation based on data obtained from the Gene Expression Omnibus (GEO) database. Then, we explored the effects of miR-483-5p on mitochondrial biogenesis, mitochondrial-dependent apoptosis, and oxidative stress levels after ischemia‒reperfusion injury in vitro and in vivo. MiR-483-5p was downregulated in PC12 cells and hippocampal samples compared with that in normal group cells and hippocampi. Overexpression of miR-483-5p increased the viability of PC12 cells after ischemia‒reperfusion injury and reduced the proportion of dead cells. A western blot analysis showed that miR-483-5p increased the protein expression of PCG-1, NRF1, and TFAM and reduced the protein expression of Bax and cleaved caspase 3, inhibiting the release of cytochrome c from mitochondria and alleviating oxidative stress injury by inhibiting the production of ROS and reducing MDA activity. We confirmed that miR-483-5p targeted TNFSF8 to regulate the AMPK/JNK pathway, thereby playing a neuroprotective role after cardiopulmonary resuscitation. Hence, this study provides further insights into strategies for inhibiting neurological impairment after cardiopulmonary resuscitation and suggests a potential therapeutic target for PCABI.

Funder

National Natural Science Foundation of China

Basic and Applied Basic Research Foundation of Guangdong Province

Shenzhen Science and Technology Innovation Program

Basic research support project of Shenzhen

Publisher

Springer Science and Business Media LLC

Subject

Cell Biology,Cellular and Molecular Neuroscience,General Medicine

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