Aldehyde dehydrogenase 2 preserves mitochondrial morphology and attenuates hypoxia/reoxygenation-induced cardiomyocyte injury

Rui Zhang; Meng-Yang Xue; Bao-Shan Liu; Wen-Jun Wang; Xin-Hui Fan; Bo-Yuan Zheng; Qiu-Huan Yuan; Feng Xu; Jia-Li Wang; Yu-Guo Chen

doi:10.5847/wjem.j.1920-8642.2020.04.007

Aldehyde dehydrogenase 2 preserves mitochondrial morphology and attenuates hypoxia/reoxygenation-induced cardiomyocyte injury

World J Emerg Med. 2020;11(4):246-254. doi: 10.5847/wjem.j.1920-8642.2020.04.007.

Authors

Rui Zhang^{1

2

3

4}, Meng-Yang Xue^{1

2

3

4}, Bao-Shan Liu^{1

2

3

4}, Wen-Jun Wang^{1

2

3

4}, Xin-Hui Fan^{1

2

3

4}, Bo-Yuan Zheng^{1

2

3

4}, Qiu-Huan Yuan^{1

2

3

4}, Feng Xu^{1

2

3

4}, Jia-Li Wang^{1

2

3

4}, Yu-Guo Chen^{1

2

3

4}

Affiliations

¹ Department of Emergency Medicine and Chest Pain Center, Qilu Hospital, Shandong University, Jinan, China.
² Shandong Provincal Clinical Research Center for Emergency and Critical Care Medicine of Shandong Province, Institute of Emergency and Critical Care Medicine of Shandong University, Qilu Hospital, Shandong University, Jinan, China.
³ Key Laboratory of Emergency and Critical Care Medicine of Shandong Province, Key Laboratory of Cardiopulmonary- Cerebral Resuscitation Research of Shandong Province, Qilu Hospital, Shandong University, Jinan, China.
⁴ The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese Ministry of Health and Chinese Academy of Medical Sciences; the State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine; Qilu Hospital, Shandong University, Jinan, China.

PMID: 33014221
PMCID: PMC7517403
DOI: 10.5847/wjem.j.1920-8642.2020.04.007

Abstract

Background: Disturbance of mitochondrial fission and fusion (termed mitochondrial dynamics) is one of the leading causes of ischemia/reperfusion (I/R)-induced myocardial injury. Previous studies showed that mitochondrial aldehyde dehydrogenase 2 (ALDH2) conferred cardioprotective effect against myocardial I/R injury and suppressed I/R-induced excessive mitophagy in cardiomyocytes. However, whether ALDH2 participates in the regulation of mitochondrial dynamics during myocardial I/R injury remains unknown.

Methods: In the present study, we investigated the effect of ALDH2 on mitochondrial dynamics and the underlying mechanisms using the H9c2 cells exposed to hypoxia/reoxygenation (H/R) as an in vitro model of myocardial I/R injury.

Results: Cardiomyocyte apoptosis was significantly increased after oxygen-glucose deprivation and reoxygenation (OGD/R), and ALDH2 activation largely decreased the cardiomyocyte apoptosis. Additionally, we found that both ALDH2 activation and overexpression significantly inhibited the increased mitochondrial fission after OGD/R. Furthermore, we found that ALDH2 dominantly suppressed dynamin-related protein 1 (Drp1) phosphorylation (Ser616) and adenosine monophosphate-activated protein kinase (AMPK) phosphorylation (Thr172) but not interfered with the expression levels of mitochondrial shaping proteins.

Conclusions: We demonstrate the protective effect of ALDH2 against cardiomyocyte H/R injury with a novel mechanism on mitochondrial fission/fusion.

Keywords: Aldehyde dehydrogenase 2; Dynamin-related protein 1; Mitochondrial dynamics; Mitochondrial fission/fusion; Myocardial hypoxia/reoxygenation injury.