Melatonin protects against diabetic cardiomyopathy through Mst1/Sirt3 signaling. Issue 2 (9th June 2017)

• Record Type: Journal Article
• Authors: Zhang, Mingming; Lin, Jie; Wang, Shanjie; Cheng, Zheng; Hu, Jianqiang; Wang, Tingting; Man, Wanrong; Yin, Tao; Guo, Wenyi; Gao, Erhe; Reiter, Russel J.; Wang, Haichang; Sun, Dongdong
• Is Part Of: Journal of pineal research. Volume 63:Issue 2(2017)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2017-06-09
• Subjects: autophagy -- diabetic cardiomyopathy -- mammalian Ste20‐like kinase 1 -- melatonin -- silent information regulator 3; Pineal gland -- Periodicals; Pineal Gland -- Periodicals; Épiphyse (Glande); Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 612.492
• DOI: 10.1111/jpi.12418
• Languages: English
• ISSNs: 0742-3098

Abstract

Abstract: This study investigated the effects of melatonin on diabetic cardiomyopathy (DCM) and determined the underlying mechanisms. Echocardiography indicated that melatonin notably mitigated the adverse left ventricle remodeling and alleviated cardiac dysfunction in DCM. The mechanisms were attributed to increased autophagy, reduced apoptosis, and alleviated mitochondrial dysfunction. Furthermore, melatonin inhibited Mst1 phosphorylation and promoted Sirt3 expression in DCM. These results indicated that melatonin may exert its effects through Mst1/Sirt3 signaling. To verify this hypothesis, a DCM model using Mst1 transgenic (Mst1 Tg) and Mst1 knockout (Mst1 −/− ) mice was constructed. As expected, melatonin increased autophagy, reduced apoptosis and improved mitochondrial biogenesis in Mst1 Tg mice subjected to DCM injury, while it had no effects on Mst1 −/− mice. In addition, cultured neonatal mouse cardiomyocytes were subjected to simulated diabetes to probe the mechanisms involved. Melatonin administration promoted autophagic flux as demonstrated by elevated LC3‐II and lowered p62 expression in the presence of bafilomycin A1. The results suggest that melatonin alleviates cardiac remodeling and dysfunction in DCM by upregulating autophagy, limiting apoptosis, and modulating mitochondrial integrity and biogenesis. The mechanisms are associated with Mst1/Sirt3 signaling.