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Oncotarget. 2017 Sep 11;8(46):80612-80624. doi: 10.18632/oncotarget.20811. eCollection 2017 Oct 6.

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

Qiao L#1,2, Guo B#1,2, Zhang H1,2, Yang R1,2, Chang L1,2, Wang Y1,2, Jin X1,2, Liu S1,2, Li Y1,2.

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Department of Cardiology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, P.R. China.
The Hebei Institute of Cardiovascular and Cerebrovascular Diseases, Shijiazhuang, Hebei, P.R. China.
Contributed equally


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.


Bmal1 gene; autophagy; cardiomyocyte injury; circadian clock; diabetic cardiomyopathy

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