Kleszczynski 2018 Int J Mol Sci

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Kleszczyński K, Bilska B, Stegemann A, Flis DJ, Ziolkowski W, Pyza E, Luger TA, Reiter RJ, Böhm M, Slominski AT (2018) Melatonin and its metabolites ameliorate UVR-induced mitochondrial oxidative stress in human MNT-1 melanoma cells. Int J Mol Sci 19:E3786.

» PMID: 30487387 Open Access

Kleszczynski K, Bilska B, Stegemann A, Flis DJ, Ziolkowski W, Pyza E, Luger TA, Reiter RJ, Boehm M, Slominski AT (2018) Int J Mol Sci

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.

Keywords: Calcium homeostasis, Catalase, Melanoma cells, Metabolites of melatonin, Mitochondria, Oxidative phosphorylation, Ultraviolet radiation Bioblast editor: Plangger M O2k-Network Lab: PL Gdansk Kaczor JJ, CZ Prague Zeman J


Labels: MiParea: Respiration, Pharmacology;toxicology 

Stress:Oxidative stress;RONS  Organism: Mouse  Tissue;cell: Liver  Preparation: Isolated mitochondria 


Coupling state: LEAK, OXPHOS  Pathway: N, NS  HRR: Oxygraph-2k 

Labels, 2018-12