The clock gene, brain and muscle Arnt-like 1, regulates autophagy in high glucose-induced cardiomyocyte injury
Metrics: PDF 1309 views | HTML 2248 views | ?
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
Yongjun Li, email: firstname.lastname@example.org
Bingyan Guo, email: email@example.com
Keywords: circadian clock, Bmal1 gene, autophagy, diabetic cardiomyopathy, cardiomyocyte injury
Received: January 30, 2017 Accepted: August 26, 2017 Published: September 11, 2017
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.
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.