Oncotarget

Research Papers:

The clock gene, brain and muscle Arnt-like 1, regulates autophagy in high glucose-induced cardiomyocyte injury

Li Qiao, Bingyan Guo, Hui Zhang, Rong Yang, Liang Chang, Yaling Wang, Xin Jin, Suyun Liu and Yongjun Li _

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Oncotarget. 2017; 8:80612-80624. https://doi.org/10.18632/oncotarget.20811

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Abstract

Li Qiao1,2,*, Bingyan Guo1,2,*, Hui Zhang1,2, Rong Yang1,2, Liang Chang1,2, Yaling Wang1,2, Xin Jin1,2, Suyun Liu1,2 and Yongjun Li1,2

1Department of Cardiology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, P.R. China

2The Hebei Institute of Cardiovascular and Cerebrovascular Diseases, Shijiazhuang, Hebei, P.R. China

*These authors contributed equally to this work

Correspondence to:

Yongjun Li, email: lyjbs2009@yeah.net

Bingyan Guo, email: gbyan2008bs@163.com

Keywords: circadian clock, Bmal1 gene, autophagy, diabetic cardiomyopathy, cardiomyocyte injury

Received: January 30, 2017     Accepted: August 26, 2017     Published: September 11, 2017

ABSTRACT

High-glucose-induced cardiomyocyte injury is the major cause of diabetic cardiomyopathy, but its regulatory mechanisms are not fully understood. Here, we report that a circadian clock gene, brain and muscle Arnt-like 1 (Bmal1), increases autophagy in high-glucose-induced cardiomyocyte injury. We constructed a hyperglycemia model with cultured cardiomyocytes from neonatal rats. High-glucose-induced inhibition of autophagy and cardiomyocyte injury were attenuated by Bmal1 overexpression and aggravated by its knockdown. Furthermore, autophagy stabilization by 3-methyladenine or rapamycin partially suppressed the effects of altered Bmal1 expression on cardiomyocyte survival. Mechanistically, Bmal1 mediated resistance to high-glucose-induced inhibition of autophagy at least partly by inhibiting mTOR signaling activity. Collectively, our findings suggest that the clock gene Bmal1 is a positive regulator of autophagy through the mTOR signaling pathway and protects cardiomyocytes against high-glucose toxicity.


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