[Frontiers in Bioscience E5, 305-315, January 1, 2013]

Cardioprotective effect of melatonin against ischaemia/reperfusion damage

Amanda Lochner1, Barbara Huisamen1, Frederic Nduhirabandi1

1Dept Biomedical Sciences, Division of Medical Physiology, Faculty of Health Sciences, University of Stellenbosch, Tygerberg, 7505, Republic of South Africa


1. Abstract
2. Introduction
3. Melatonin and the heart
4. Melatonin and ischaemia/reperfusion injury
5. Melatonin signaling
5.1 .Role of Melatonin receptors
5.2. Intracellular signaling
5.3.Anti-adrenergic effects
6. Events downstream of melatonin receptor stimulation
6.1 .RISK and SAFE pathways
6.2. Melatonin and mitochondria
6.2.1. Mitochondrial function
6.2.2. Mitochondrial permeability transition pore
7. Myocardial substrate metabolism
8. Melatonin and intracellular Ca2+ handling
8.1. Melatonin and sarcoplasmic reticulum
8.2. Melatonin and ANP
9. Conclusions
10. Acknowledgment
11. References
12. Abbreviations
13. Keywords


Melatonin (N-acetyl-5-methoxytryptamine) has been shown by several workers to protect the heart against ischaemia/reperfusion damage. Melatonin, both in the picomolar and micromolar range, significantly reduces infarct size and improves functional recovery during reperfusion. This may be due to its free radical scavenging and anti-oxidant effects, while the melatonin receptor and its marked anti-adrenergic actions may also be involved. The latter is mediated by nitric oxide (NO), guanylyl cyclase and protein kinase C (PKC). Melatonin-induced cardioprotection is associated with activation of protein kinase B (PKB), extracellular signal-regulated kinase (ERK1/2) (the Reperfusion Injury Salvage Kinase (RISK) pathway) and signal activator and transducer 3 (STAT-3) (the Survivor Activating Factor Enhancement (SAFE) pathway) during reperfusion and inhibition of the mitochondrial permeability transition pore (MPTP). Very little is known about the effect of melatonin on myocardial substrate metabolism. Melatonin was demonstrated to be involved in the regulation of whole body glucose homeostasis via its effects on pancreatic insulin secretion and may thus indirectly affect myocardial substrate metabolism in a circadian manner.