Melatonin protects against diabetic cardiomyopathy through Mst1/Sirt3 signaling.

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.

• Authors: Mingming Zhang, Jie Lin, Shanjie Wang, Zheng Cheng, Jianqiang Hu, Tingting Wang, Wanrong Man, Tao Yin, Wenyi Guo, Erhe Gao, Russel J Reiter, Haichang Wang, Dongdong Sun
• Journal: Journal of pineal research (J Pineal Res) Vol. 63 Issue 2 (Sep 2017) ISSN: 1600-079X [Electronic] England
• PMID: 28480597 (Publication Type: Journal Article)
• Copyright: © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Chemical References

• Macrolides
• Map1lc3b protein, mouse
• Microtubule-Associated Proteins
• Proto-Oncogene Proteins
• Sirt3 protein, mouse
• macrophage stimulating protein
• bafilomycin A
• Hepatocyte Growth Factor
• Sirtuin 3
• Melatonin

Topics

• Animals
• Diabetic Cardiomyopathies (genetics, metabolism, pathology, prevention & control)
• Gene Expression Regulation (drug effects)
• Hepatocyte Growth Factor (genetics, metabolism)
• Macrolides (pharmacology)
• Melatonin
• Mice
• Mice, Knockout
• Microtubule-Associated Proteins (biosynthesis, genetics)
• Mitochondria, Heart (genetics, metabolism, pathology)
• Myocytes, Cardiac (metabolism, pathology)
• Phosphorylation (drug effects, genetics)
• Proto-Oncogene Proteins (genetics, metabolism)
• Signal Transduction (drug effects, genetics)
• Sirtuin 3 (genetics, metabolism)