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The mitochondria-targeted antioxidant MitoQ ameliorates myocardial ischemia–reperfusion injury by enhancing PINK1/Parkin-mediated mitophagy in type 2 diabetic rats

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Cell Stress and Chaperones Aims and scope

Abstract

Type 2 diabetic hearts are more vulnerable to myocardial ischemia reperfusion (MIR) injury, which involves decreased mitophagy status with unknown mechanisms. MitoQ, a mitochondria-targeted antioxidant, has been shown to have protection against ischemia reperfusion injury through upregulating mitophagy. The aim of this study was to investigate the effects of MitoQ on myocardium during MIR injury in type 2 diabetes (T2D). Herein, this study discovered that type 2 diabetic hearts with PINK1/Parkin downregulation suffered more MIR injury accompanied by reduced mitophagy. Treatment with MitoQ significantly decreased the levels of CK-MB, LDH, myocardial infarction, myocardial pathological damage, and cardiomyocytes apoptosis, while it improved cardiac function, mitophagy status, and PINK1/Parkin pathway in vivo study. Furthermore, MitoQ significantly reduced high glucose/high fat and hypoxia/reoxygenation induced injury in H9C2 cells as evidenced by reduced cardiomyocytes apoptosis and ROS production, and increased cell viability, the level of mitochondrial membrane potential, PINK1/Parkin expression. However, mitochondrial division inhibitor (mdivi-1), an inhibitor of mitophagy, reversed the improvement and protein expression levels of PINK1/Parkin pathway in vitro models. In conclusion, MIR induced more severe damage in T2D by reduction of mitophagy. MitoQ can confer cardioprotection following MIR in T2D by mitophagy up-regulation via PINK1/Parkin pathway.

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Data availability

All the data can be obtained from the corresponding authors.

Abbreviations

CCK-8:

Cell counting kit-8

CK-MB:

Creatine kinase-MB

DCFH-DA:

Dichloro-dihydro-fluorescein diacetate

DMEM:

Dulbecco’s modified Eagle’s medium

FBG:

Fasting blood glucose

FBS:

Fetal bovine serum

HG:

High glucose

HR:

Hypoxia/reoxygenation

HFD:

High-fat diet

HR:

Heart rate

LAD:

Left anterior descending coronary artery

LDH:

Lactate dehydrogenase

LVSP:

Left ventricular systolic blood pressure

 + dp/dtmax:

LVSP maximum increase rates

 − dp/dtmax:

LVSP maximum decrease rates

MIR:

Myocardial ischemia reperfusion

TEM:

Transmission electron microscopy

T2D:

Type 2 diabetes

7-AAD:

7-Amino-actinomycin

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Acknowledgements

The authors would like to thank the central laboratory at Renmin Hospital of Wuhan University (Wuhan, Hubei, China) for their support of our study.

Funding

This study was supported by grants from the National Natural Science Foundation of China (NSFC 81970722, 81671891, and 81901947) and the Basic Scientific Research of Central University Fund (2042019kf0056).

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  1. Yelong Ji and Yan Leng equally contributed to this article.

Authors and Affiliations

  1. Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei Province, China

    Yelong Ji, Yan Leng, Shaoqing Lei, Zhen Qiu, Hao Ming, Yi Zhang, Aining Zhang, Yang Wu & Zhongyaun Xia

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  1. Yelong Ji
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  2. Yan Leng
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Contributions

Zhongyuan Xia designed the overall project and supervised the study; Xiazhong Yuan, Yelong Ji, Yang Wu, and Yan Leng designed the experiments; Yelong Ji and Zhen Qiu performed in vivo experiments; Yelong Ji and Yi Zhang performed in vitro experiment; Yelong Ji, Hao Ming, and Aining Zhang performed formal analysis; Yelong Ji, Yang Wu, and Yan Leng wrote the paper with input from other authors. Zhongyuan Xia and Shaoqing Lei reviewed and supervised the paper. All authors have read and agreed to the published version of the manuscript.

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Correspondence to Yang Wu or Zhongyaun Xia.

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Ji, Y., Leng, Y., Lei, S. et al. The mitochondria-targeted antioxidant MitoQ ameliorates myocardial ischemia–reperfusion injury by enhancing PINK1/Parkin-mediated mitophagy in type 2 diabetic rats. Cell Stress and Chaperones 27, 353–367 (2022). https://doi.org/10.1007/s12192-022-01273-1

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