Int J Med Sci 2020; 17(17):2869-2878. doi:10.7150/ijms.49849 This issue

Research Paper

Deletion of mitochondrial uncoupling protein 2 exacerbates mitophagy and cell apoptosis after cerebral ischemia and reperfusion injury in mice

Maotao He1,2,3, Ting Zhang2, Yucheng Fan2, Yanmei Ma2, Jianzhong Zhang2, Li Jing2✉, P. Andy Li3✉

1. Department of Pathology, General Hospital of Ningxia Medical University, Yinchuan, Ningxia 750004, China.
2. School of Basic Medical Sciences, Department of Pathology, Ningxia Medical University; Ningxia Key Laboratory of Vascular Injury and Repair, Yinchuan, Ningxia 750004, China.
3. Department of Pharmaceutical Sciences, Biomanufacturing Research Institute and Technological Enterprise (BRITE), College of Health and Sciences, North Carolina Central University, Durham, NC 27707, USA.

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Citation:
He M, Zhang T, Fan Y, Ma Y, Zhang J, Jing L, Li PA. Deletion of mitochondrial uncoupling protein 2 exacerbates mitophagy and cell apoptosis after cerebral ischemia and reperfusion injury in mice. Int J Med Sci 2020; 17(17):2869-2878. doi:10.7150/ijms.49849. Available from https://www.medsci.org/v17p2869.htm

File import instruction

Abstract

Objective: Uncoupling protein 2 (UCP2) is a member of inner mitochondrial membrane proteins and deletion of UCP2 exacerbates brain damage after cerebral ischemia/reperfusion (I/R). Nevertheless, its functional role during cerebral I/R is not entirely understood. The objective of present study was to explore the influence of UCP2 deletion on mitochondrial autophagy (mitophagy) and mitochondria-mediated cell death pathway after cerebral I/R.

Methods: UCP2-/- and wildtype (WT) mice were subjected to 60 min middle cerebral artery occlusion (MCAO) and allowed reperfusion for 24 hours. Infarct volume and histological outcomes were assessed, reactive oxygen species (ROS) and autophagy markers were measured, and mitochondrial ultrastructure was examined.

Results: Deletion of UCP2 enlarged infarct volume, increased numbers of necrotic and TUNEL positive cells, and significantly increased pro-apoptotic protein levels in UCP2-/- mice compared with WT mice subjected to the same duration of I/R. Further, deletion of UCP2 increased ROS production, elevated LC3, Beclin1 and PINK1, while it suppressed p62 compared with respective WT ischemic controls. Electron microscopic study demonstrated the number of autophagosomes was higher in the UCP2-/- group, compared with the WT group.

Conclusions: It is concluded that deletion of UCP2 exacerbates cerebral I/R injury via reinforcing mitophagy and cellular apoptosis in mice.

Keywords: uncoupling protein 2, cerebral ischemia/reperfusion, mitophagy, autophagy, apoptosis, ROS