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Biochem Biophys Res Commun. 2019 Apr 23;512(1):125-130. doi: 10.1016/j.bbrc.2019.03.008. Epub 2019 Mar 12.

Cardioprotective effects of constitutively active MEK1 against H2O2-induced apoptosis and autophagy in cardiomyocytes via the ERK1/2 signaling pathway.

Author information

1
Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830054, PR China; Xinjiang Key Laboratory of Cardiovascular Disease Research, Urumqi, 830054, PR China; Department of Nephrology, Fifth Affiliated Hospital of Xinjiang Medical University, Urumqi, 830000, PR China.
2
Xinjiang Key Laboratory of Cardiovascular Disease Research, Urumqi, 830054, PR China; Clinical Medical Research Institute of Xinjiang Medical University, Urumqi, 830054, PR China.
3
Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830054, PR China; Xinjiang Key Laboratory of Cardiovascular Disease Research, Urumqi, 830054, PR China.
4
Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830054, PR China.
5
Xinjiang Key Laboratory of Cardiovascular Disease Research, Urumqi, 830054, PR China; Clinical Medical Research Institute of Xinjiang Medical University, Urumqi, 830054, PR China; State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Urumqi, 830000, PR China; Xinjiang Key Laboratory of Medical Animal Model Research, Urumqi, 830054, PR China; Baker Heart and Diabetes Institute, Department of Surgery, Central Clinical School, Monash University, Melbourne, Australia.
6
Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830054, PR China. Electronic address: myt-xj@163.com.
7
Xinjiang Key Laboratory of Cardiovascular Disease Research, Urumqi, 830054, PR China; Clinical Medical Research Institute of Xinjiang Medical University, Urumqi, 830054, PR China. Electronic address: chenbangdang@126.com.

Abstract

Oxidative stress injury is one of the main mechanisms of ischemia-reperfusion (I/R) injury. The extracellular signal-regulated kinase (ERK1/2) pathway plays an important role in cardioprotective during acute myocardial infarction. In this study, we used constitutively active MEK1 gene (CaMEK) transfection strategy to investigate whether CaMEK provides a protective effect against apoptosis and autophagy induced by Hydrogen peroxide (H2O2) in neonatal rat cardiac ventricular cardiomyocytes (NCMs) and the underlying mechanisms. As a result, CaMEK attenuated H2O2-induced apoptosis and cytotoxicity in NCMs, evidenced by decreased apoptotic cells and the ratio of Bax/Bcl-2, increased the mitochondrial membrane potential (Δψm) and cell vitality and reduced the level of lactate dehydrogenase (LDH). Further studies revealed that CaMEK attenuated H2O2-induced autophagy, evidenced by the decreased LC3-Ⅱ/LC3-Ⅰratio and SQSTM1/p62 (p62) degradation. Furthermore, we demonstrated that CaMEK phosphorylated the ERK1/2 pathway-related proteins, ERK1/2, p70S6K and GSK3β, in NCMs with H2O2 stimulation. In contrast, these effects could be reversed by co-treatment with the ERK1/2 inhibitor, PD98059. These results suggest that CaMEK plays an important role in protecting cardiomyocytes against H2O2-induced injury and autophagy in NCMs via ERK1/2 pathway. Therefore, transfection of CaMEK may provide a hopeful therapeutic strategy for I/R.

KEYWORDS:

Apoptosis; Autophagy; Constitutively active MEK1 gene; Extracellular signal-regulated kinase; Hydrogen peroxide; Neonatal rat cardiac ventricular cardiomyocytes

PMID:
30876692
DOI:
10.1016/j.bbrc.2019.03.008
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