Melatonin ameliorates myocardial apoptosis by suppressing endoplasmic reticulum stress in rats with long-term diabetic cardiomyopathy

Abstract

The effects of melatonin (MLT), which exerts cardioprotective effects against myocardial apoptosis, in long-term diabetic cardiomyopathy are not currently well defined. The present study aimed to investigate how MLT protects the heart through modulating myocardial apoptosis in rats with type 2 diabetes mellitus (DM). In total, 36 rats were randomly divided into three groups, including control (n=12), DM (n=12) and DM + MLT (n=12) groups. The results demonstrated that, in DM rats, a significant increase was observed in the serum fasting blood glucose and lipid levels, in addition to insulin resistance and cardiac dysfunction, which were attenuated in DM rats treated with MLT. Additionally, cellular apoptosis in rats with DM was increased, and the expression of Bcl-2 was downregulated, while levels of Bcl-2-associated X and caspase-3 were upregulated, and these observations were reversed by MLT, as determined by TUNEL and western blot analysis, respectively. As increased endoplasmic reticulum (ER) stress induced by hyperglycemia is reported to be a factor for apoptosis, the present study also determined the expression of proteins associated with ER stress in cardiac tissues following MLT treatment by western blotting. The results further indicated that MLT decreased the expression of ER stress hallmarks, including CCAAT/enhancer-binding protein homologous protein, glucose-regulated protein 78, protein kinase RNA-like endoplasmic reticulum kinase (PERK) and activating transcription factor 6α in cardiac tissues. In conclusion, the results of the present study indicate that MLT may protect heart by ameliorating cardiac ER stress-induced apoptosis in diabetic cardiomyopathy.