Melatonin elevates apoptosis in human platelets via ROS mediated mitochondrial damage

Girish, K. S. and Paul, M. and Thushara, R. M. and Hemshekhar, M. and Shanmuga Sundaram, M. and Rangappa, K. S. and Kemparaju, K. (2013) Melatonin elevates apoptosis in human platelets via ROS mediated mitochondrial damage. Biochemical and Biophysical Research Communications, 438 (1). pp. 198-204.

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Official URL: http://doi.org/10.1016/j.bbrc.2013.07.053

Abstract

Melatonin is a pineal hormone that regulates circadian and seasonal rhythms. The chronobiotic role of melatonin corresponds with a repertoire of pharmacological properties. Besides, it has a wide range of therapeutic applications. However, recent studies have demonstrated its direct interaction with platelets: at physiological concentration it promotes platelet aggregation; on the other hand, at pharmacological doses it raises intracellular Ca2+ leading to platelet activation, thrombus formation and cardiovascular disorders. In order to further probe its effects on platelets, the current study targeted platelet apoptosis and melatonin was found to stimulate apoptosis. The mitochondrial pathway of apoptosis was mainly investigated because of its susceptibility to oxidative stress-inducing factors including therapeutic and dietary elements. Melatonin significantly increased the generation of intracellular ROS and Ca2+, facilitating mitochondrial membrane depolarization, cytochrome c release, caspase activation, protein phosphorylation and phosphatidylserine externalization. Further, the overall toxicity of melatonin on platelets was confirmed by MTT and lactate dehydrogenase assays. The elevated rate of platelet apoptosis has far reaching consequences including thrombocytopenia. Besides, platelets undergoing apoptosis release microparticles, which fuel thrombus formation and play a significant role in the pathophysiology of a number of diseases. In many parts of the world melatonin is an over-the-counter dietary supplement and alternative medicine. Since, melatonin displays platelet proapoptotic effect at a concentration attainable through therapeutic dosage, the present study sends a warning signal to the chronic use of melatonin as a therapeutic drug and questions its availability without a medical prescription.

Item Type: Article
Uncontrolled Keywords: article, human, human tissue, priority journal, controlled study, hydrogen peroxide, oxidative stress, reactive oxygen metabolite, cytotoxicity, Humans, Hydrogen Peroxide, lactate dehydrogenase, human cell, protein expression, Cells, Cultured, Reactive Oxygen Species, apoptosis, Apoptosis, normal human, melatonin, Mitochondria, Mitochondrial damage, protein phosphorylation, caspase 9, caspase 3, mitochondrial membrane potential, Blood Platelets, calcium ion, cytochrome c, enzyme activation, phosphatidylserine, thrombocyte, thrombocyte rich plasma, thrombocytopenia, calcium cell level, protein secretion, Melatonin, Caspases, cell membrane depolarization, Platelet apoptosis, cell assay, cell stimulation, Intracellular calcium, Mitochondrial Degradation
Subjects: C Chemical Science > Biochemistry
C Chemical Science > Chemistry
Divisions: Department of > Biochemistry
Department of > Chemistry
Depositing User: Arshiya Kousar
Date Deposited: 19 Sep 2019 10:10
Last Modified: 19 Sep 2019 10:10
URI: http://eprints.uni-mysore.ac.in/id/eprint/7979

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