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Regulatory effect of the zinc transporter Zip2 on cardiomyocyte mitochondrial respiration function after cardiac ischemia-reperfusion injury in mice

WANG Li-Yan, CHENG Xin-Xin, XU Zhe-Long^*

Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China

Abstract

The aim of the present study was to investigate the effect of zinc transporter Zip2 (SLC39A2) on mitochondrial respiration during myocardial ischemia/reperfusion (I/R) and the underlying mechanisms. An in vivo myocardial I/R model was established in mice by ligation of left anterior descending coronary artery. Cardiac zinc concentration was measured by inductively coupled plasma- optical emission spectrometer (ICP-OES), and the mitochondrial respiratory function and oxidative phosphorylation were determined by high-resolution respirometry (Oxygraph-2K). The phosphorylation levels of STAT3 and ERK in myocardial tissue were detected by Western blot. The results showed that, compared with the sham group, cardiac zinc concentration in myocardium was decreased in wild-type mice and further reduced in Zip2 knockout mice after I/R. Mitochondrial respiratory control rate (RCR) and oxidative phosphorylation were decreased in Zip2 knockout mice and worsened by I/R. Phosphorylation levels of STAT3 (Ser727) and ERK were significantly decreased in Zip2 knockout mice after I/R. In I/R myocardial tissue, STAT3 overexpression significantly improved the mitochondrial respiratory function, while STAT3 dominant negative mutant (STAT3 S727A) inhibited mitochondrial respiratory function. Moreover, the impairment of mitochondrial function by Zip2 knockout was reversed by STAT3 overexpression. These results suggest that Zip2 regulates mitochondrial respiration via phosphorylation of STAT3 during myocardial I/R, which may represent the underlying mechanism of Zip2 cardioprotection against I/R injury.

Key words: Zinc; zinc transporter Zip2; ischemia/reperfusion injury; STAT3; mitochondrial respiration

Received: 2019-11-19　　Accepted: 2020-03-20

Corresponding author: 徐哲龙　　E-mail: zxu@tmu.edu.cn

DOI: 10.13294/j.aps.2020.0041

Citing This Article：

WANG Li-Yan, CHENG Xin-Xin, XU Zhe-Long. Regulatory effect of the zinc transporter Zip2 on cardiomyocyte mitochondrial respiration function after cardiac ischemia-reperfusion injury in mice. Acta Physiol Sin 2020; 72 (4): 433-440 (in Chinese with English abstract).