Research Paper|Volume 13, Issue 18|pp 22188—22207

Cx32 inhibits the autophagic effect of Nur77 in SH-SY5Y cells and rat brain with ischemic stroke

Fengfeng Ping³, Chao Zhang³, Xue Wang⁴, Yan Wang², Danli Zhou², Jing Hu², Yanhua Chen², Jingjing Ling², Jia Zhou¹

¹State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 211198, China
²Department of Good Clinical Practice, The Affiliated Wuxi Children's Hospital of Nanjing Medical University, Wuxi 214023, China
³Department of Reproductive Medicine, Wuxi People's Hospital Affiliated to Nanjing Medical University, Wuxi 214023, China
⁴Wuxi School of Medicine, Jiangnan University, Wuxi 214122, China

* Equal contribution

# Co-first author

Received: April 16, 2020Accepted: September 2, 2021Published: September 22, 2021

https://doi.org/10.18632/aging.203526

Copyright: © 2021 Ping et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

The pathogenesis of cerebral ischemia-reperfusion (I/R) is complex. Cx32 expression has been reported to be up-regulated in ischemic lesions of aged human brain. Nevertheless, the function of Cx32 during cerebral I/R is poorly understood. Autophagy is of vital importance in the pathogenesis of cerebral I/R. In the current study, we found that oxygen-glucose deprivation/reoxygenation (OGD/R) or I/R insult significantly induced the up-regulation of Cx32 and activation of autophagy. Inhibition of Cx32 alleviated OGD/R or I/R injury, and further activated autophagy. In addition, Nur77 expression was found to be up-regulated after OGD/R or I/R. After inhibiting Cx32, the expression of Nur77 was further increased and Nur77 was translocated from nucleus to mitochondrial. Inhibition of Cx32 also activated mitophagy by promoting autophagosome formation and up-regulating the expression of mitochondrial autophagy marker molecules. Of note, in the siNur77-transfected cells, the number of dysfunctional mitochondrial was increased, and mitophagy was suppressed, which aggravated OGD/R-induced neuronal injury. In conclusion, Cx32 might act as a regulatory factor of Nur77 controlling neuronal autophagy in the brains. Understanding the mechanism of this regulatory pathway will provide new insight into the role Cx32 and Nur77 in cerebral ischemia, offering new opportunities for therapeutics.