Abstract
Melatonin (Mel) is the major biologically active molecule secreted by the pineal gland. Mel and its metabolites, 6-hydroxymelatonin (6(OH)Mel) and 5-methoxytryptamine (5-MT), possess a variety of functions, including the scavenging of free radicals and the induction of protective or reparative mechanisms in the cell. Their amphiphilic character allows them to cross cellular membranes and reach subcellular organelles, including the mitochondria. Herein, the action of Mel, 6(OH)Mel, and 5-MT in human MNT-1 melanoma cells against ultraviolet B (UVB) radiation was investigated. The dose of 50 mJ/cm2 caused a significant reduction of cell viability up to 48%, while investigated compounds counteracted this deleterious effect. UVB exposure increased catalase activity and led to a simultaneous Ca++ influx (16%), while tested compounds prevented these disturbances. Additional analysis focused on mitochondrial respiration performed in isolated mitochondria from the liver of BALB/cJ mice where Mel, 6(OH)Mel, and 5-MT significantly enhanced the oxidative phosphorylation at the dose of 10−6 M with lower effects seen at 10−9 or 10−4 M. In conclusion, Mel, 6(OH)Mel and 5-MT protect MNT-1 cells, which express melatonin receptors (MT1 and MT2) against UVB-induced oxidative stress and mitochondrial dysfunction, including the uncoupling of oxidative phosphorylation.
Highlights
Melatonin (N-acetyl-5-methoxytryptamine) is a ubiquitous physiological mediator that is found throughout the evolutionary scale of animals and is in plants and unicellular organisms [1,2,3,4,5]
Mitochondria are the organelles with the highest production rate of reactive oxygen/nitrogen species (ROS/RNS), which are attenuated by melatonin [31] through stimulation of the activity of anti-oxidative enzymes such as catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD) [32], heme oxygenase-1 (HO-1), γ-glutamylcysteine synthetase (γ-GCS), and NADPH:quinone dehydrogenase-1 (NQO-1), which were induced via activation of nuclear erythroid 2-related factor (Nrf2) [26,33]
It is recognized that mitochondria are the main target of the environmental stress factors, one of them represented by ultraviolet radiation (UVR)
Summary
Melatonin (N-acetyl-5-methoxytryptamine) is a ubiquitous physiological mediator that is found throughout the evolutionary scale of animals and is in plants and unicellular organisms [1,2,3,4,5]. Exposure of the skin to UVB induces direct DNA damage [35] such as cyclobutane pyrimidine dimers (CPD) and pyrimidine photoproducts (6-4-PPs) [36,37,38,39] with the additional production of reactive oxygen species (ROS) induced by UVA [40,41]. These changes have detrimental effects that include carcinogenesis, cell senescence, and other skin pathologies [42]. We tested the effect of compounds themselves on the bioenergetics of native isolated mitochondria evaluating their respiratory capacity to understand a “real face” of melatonin’s capability to stabilize mitochondrial homeostasis
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