Melatonin and its metabolites ameliorate UVR-induced mitochondrial oxidative stress in human MNT-1 melanoma cells

Konrad Kleszczyński, Bernadetta Bilska, Agatha Stegemann, Damian Jozef Flis, Wieslaw Ziolkowski, Elżbieta Pyza, Thomas A. Luger, Russel J Reiter, Markus Böhm, Andrzej T. Slominski

Research output: Contribution to journalArticle

8 Scopus citations

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.

Original languageEnglish (US)
Article number3786
JournalInternational Journal of Molecular Sciences
Volume19
Issue number12
DOIs
StatePublished - Dec 1 2018

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Keywords

  • Calcium homeostasis
  • Catalase
  • Melanoma cells
  • Metabolites of melatonin
  • Mitochondria
  • Oxidative phosphorylation
  • Ultraviolet radiation

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

Cite this

Kleszczyński, K., Bilska, B., Stegemann, A., Flis, D. J., Ziolkowski, W., Pyza, E., Luger, T. A., Reiter, R. J., Böhm, M., & Slominski, A. T. (2018). Melatonin and its metabolites ameliorate UVR-induced mitochondrial oxidative stress in human MNT-1 melanoma cells. International Journal of Molecular Sciences, 19(12), [3786]. https://doi.org/10.3390/ijms19123786