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

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

Journal

World journal of emergency medicine
ISSN: 1920-8642
Titre abrégé: World J Emerg Med
Pays: China
ID NLM: 101549691

Informations de publication

Date de publication:
2020
Historique:
entrez: 5 10 2020
pubmed: 6 10 2020
medline: 6 10 2020
Statut: ppublish

Résumé

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

Sections du résumé

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

Identifiants

DOI: 10.5847/wjem.j.1920-8642.2020.04.007 PMID: 33014221 PMC: PMC7517403
pubmed: 33014221
doi: 10.5847/wjem.j.1920-8642.2020.04.007
pii: WJEM-11-246
pmc: PMC7517403
doi:

Types de publication

Journal Article

Langues

eng

Pagination

246-254

Informations de copyright

Copyright: © 2020 World Journal of Emergency Medicine.

Déclaration de conflit d'intérêts

Conflicts of interest: The authors declare that there is no conflict of interest.

Références

Circulation. 2010 May 11;121(18):2012-22
pubmed: 20421521
J Am Heart Assoc. 2013 Oct 08;2(5):e000461
pubmed: 24103571
Shock. 2016 Feb;45(2):192-7
pubmed: 26555744
Cardiovasc Res. 2010 Oct 1;88(1):16-29
pubmed: 20631158
FEBS Lett. 1987 May 11;215(2):233-6
pubmed: 3582651
Biochim Biophys Acta. 2016 Dec;1862(12):2199-2210
pubmed: 27412473
Int J Cardiol. 2018 Apr 15;257:150-159
pubmed: 29506687
Front Pharmacol. 2016 Apr 21;7:101
pubmed: 27148058
J Cell Physiol. 2018 Aug;233(8):5589-5597
pubmed: 29528108
Biochim Biophys Acta. 2013 Jan;1833(1):233-41
pubmed: 22450031
Free Radic Biol Med. 2013 Dec;65:371-379
pubmed: 23867156
Physiol Rep. 2017 Jun;5(11):
pubmed: 28576854
J Clin Invest. 2013 Jan;123(1):92-100
pubmed: 23281415
Free Radic Biol Med. 2011 Nov 1;51(9):1736-48
pubmed: 21871561
Proc Natl Acad Sci U S A. 2013 Apr 9;110(15):5969-74
pubmed: 23530233
Annu Rev Physiol. 2019 Feb 10;81:1-17
pubmed: 30256725
Nat Commun. 2014 Apr 07;5:3596
pubmed: 24710105
J Cell Mol Med. 2017 Nov;21(11):2643-2653
pubmed: 28941171
J Cell Sci. 2017 Sep 15;130(18):2953-2960
pubmed: 28842472
Trends Endocrinol Metab. 2015 Aug;26(8):422-9
pubmed: 26160707
Nat Cell Biol. 2011 Feb;13(2):132-41
pubmed: 21258367
J Physiol. 2006 Jul 1;574(Pt 1):95-112
pubmed: 16690706
Front Pharmacol. 2019 Feb 12;10:61
pubmed: 30809145
Am J Physiol Heart Circ Physiol. 2007 Aug;293(2):H1107-14
pubmed: 17496214
Science. 2011 Jan 28;331(6016):456-61
pubmed: 21205641
Science. 2008 Sep 12;321(5895):1493-5
pubmed: 18787169
Science. 2016 Jan 15;351(6270):275-281
pubmed: 26816379
Essays Biochem. 2018 Jul 20;62(3):341-360
pubmed: 30030364
J Clin Invest. 2009 May;119(5):1275-85
pubmed: 19349686
Theranostics. 2018 Jan 1;8(4):1027-1041
pubmed: 29463997
Nat Rev Dis Primers. 2019 Jun 6;5(1):39
pubmed: 31171787
Cell Res. 2013 Jul;23(7):915-30
pubmed: 23689279
FASEB J. 2014 Jan;28(1):316-26
pubmed: 24076965
Crit Care Med. 2016 Jul;44(7):e544-52
pubmed: 26757166
Cell Death Differ. 2017 Jun;24(6):1111-1120
pubmed: 28498369
J Cardiovasc Pharmacol. 2014 Jun;63(6):477-87
pubmed: 24477044
Cell Death Dis. 2015 Dec 03;6:e2007
pubmed: 26633713
N Engl J Med. 2007 Sep 13;357(11):1121-35
pubmed: 17855673
Biochem J. 2006 Apr 1;395(1):57-64
pubmed: 16321138
N Engl J Med. 2013 Dec 5;369(23):2236-51
pubmed: 24304053
Biochim Biophys Acta. 1996 May 31;1301(1-2):67-75
pubmed: 8652652
Eur Heart J. 2011 Apr;32(8):1025-38
pubmed: 20705694

Auteurs

Rui Zhang (R)

Department of Emergency Medicine and Chest Pain Center, Qilu Hospital, Shandong University, Jinan, China.
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.
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.
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.

Meng-Yang Xue (MY)

Department of Emergency Medicine and Chest Pain Center, Qilu Hospital, Shandong University, Jinan, China.
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.
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.
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.

Bao-Shan Liu (BS)

Department of Emergency Medicine and Chest Pain Center, Qilu Hospital, Shandong University, Jinan, China.
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.
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.
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.

Wen-Jun Wang (WJ)

Department of Emergency Medicine and Chest Pain Center, Qilu Hospital, Shandong University, Jinan, China.
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.
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.
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.

Xin-Hui Fan (XH)

Department of Emergency Medicine and Chest Pain Center, Qilu Hospital, Shandong University, Jinan, China.
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.
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.
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.

Bo-Yuan Zheng (BY)

Department of Emergency Medicine and Chest Pain Center, Qilu Hospital, Shandong University, Jinan, China.
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.
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.
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.

Qiu-Huan Yuan (QH)

Department of Emergency Medicine and Chest Pain Center, Qilu Hospital, Shandong University, Jinan, China.
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.
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.
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.

Feng Xu (F)

Department of Emergency Medicine and Chest Pain Center, Qilu Hospital, Shandong University, Jinan, China.
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.
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.
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.

Jia-Li Wang (JL)

Department of Emergency Medicine and Chest Pain Center, Qilu Hospital, Shandong University, Jinan, China.
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.
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.
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.

Yu-Guo Chen (YG)

Department of Emergency Medicine and Chest Pain Center, Qilu Hospital, Shandong University, Jinan, China.
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.
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.
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.

Classifications MeSH