ABC | Volume 110, Nº1, January 2018

Original Article Hu et al Melatonin’s modulation on calcium in cardiomyocytes Arq Bras Cardiol. 2018; 110(1):44-51 1. HausenloyDJ,YellonDM.Myocardialischemia-reperfusioninjury:aneglected therapeutictarget.JClinInvest.2013;123(1):92-100.doi:10.1172/JCI62874. 2. Morel O, Perret T, Delarche N, Labeque JN, Jouve B, Elbaz M, et al. Pharmacological approaches to reperfusion therapy. Cardiovasc Res. 2012;94(2):246-52. doi: 10.1093/cvr/cvs114. 3. Ibanez B, Heusch G, Ovize M, Van de Werf F. Evolving therapies for myocardial ischemia/reperfusion injury. J Am Coll Cardiol. 2015;65(14):1454-71. doi: 10.1016/j.jacc.2015.02.032. 4. Chen M, Zheng YY, Song YT, Xue JY, Liang ZY, Yan XX, et al. Pretreatment with low-dosegadoliniumchlorideattenuatesmyocardialischemia/reperfusioninjury inrats.ActaPharmacolSin.2016;37(4):453-62.doi:10.1038/aps.2015.156. 5. Bulluck H, Yellon DM, Hausenloy DJ. Reducing myocardial infarct size: challenges and future opportunities. 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J Pineal Res. 2013;55(3):275-86. doi: 10.1111/jpi.12070. 19. YeungHM,HungMW,FungML.Melatoninamelioratescalciumhomeostasis in myocardial and ischemia-reperfusion injury in chronically hypoxic rats. J Pineal Res. 2008;45(4):373-82. doi: 10.1111/j.1600-079X.2008.00601.x. References the expression of IP3R. Pretreatment of PD98059 reversed the effect of melatonin on expression of IP3R and SERCA2a. In vivo, myocardial IP3R level is reduced and SERCA2a expression is increased by pretreatment of melatonin, however, PD98059 reversed the effect of melatonin on expression of IP3R and SERCA2a. Melatonin in the dose used in the study did not show obvious side effects compared with other groups. In vivo results further confirmed that melatonin regulates the expression of IP3R and SERCA2a via ERK1. From the above results, it is reasonable to infer that melatonin could protect cardiomyocytes against reperfusion injury through affecting IP3R and SERCA2a expression to inhibit calcium overload via ERK1 pathway. Conclusion Melatonin can protect cardiomyocytes against reperfusion injury through modulation of IP3R and SERCA2a attenuating calcium overload via ERK1 pathway. Improved calcium homeostasis followed by preserved function and structure of cardiomyocytes can decrease cardiomyocytes apoptosis and improve heart function. The present study provide more evidence for the use of melatonin to protect cardiac function in patients with STEMI undergoing myocardial reperfusion therapy. Author contributions Conception and design of the research: Hu S, Zhu P, Zhou H, Zhang Y, Chen Y; Acquisition of data: Hu S, Zhu P, Zhou H, Zhang Y; Analysis and interpretation of the data, Statistical analysis andCritical revisionof themanuscript for intellectual content:HuS, ZhouH;Obtaining financing andWriting of themanuscript: Hu S. Potential Conflict of Interest No potential conflict of interest relevant to this article was reported. Sources of Funding This study was funded by National Natural Science Foundation of China (Nº.81770237) and partially funded by China Postdoctoral Science Foundation. Study Association This study is not associatedwith any thesis or dissertationwork. Ethics approval and consent to participate This study was approved by the Ethics Committee on Animal Experiments of the Chinese PLA General Hospital. 50

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