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Int J Mol Sci. 2018 Nov 28;19(12). pii: E3786. doi: 10.3390/ijms19123786.

Melatonin and Its Metabolites Ameliorate UVR-Induced Mitochondrial Oxidative Stress in Human MNT-1 Melanoma Cells.

Author information

1
Department of Dermatology, University of Münster, Von-Esmarch-Str. 58, 48149 Münster, Germany. konrad.kleszczynski@ukmuenster.de.
2
Department of Cell Biology and Imaging, Institute of Zoology and Biomedical Research, Jagiellonian University, Gronostajowa 9, 30-387 Kraków, Poland. bernadetta.bilska@doctoral.uj.edu.pl.
3
Department of Dermatology, University of Münster, Von-Esmarch-Str. 58, 48149 Münster, Germany. agathastegemann@gmail.com.
4
Department of Bioenergetics and Nutrition, Gdańsk University of Physical Education and Sport, Górski Str. 1, 80-336 Gdańsk, Poland. damian.flis@awf.gda.pl.
5
Department of Bioenergetics and Nutrition, Gdańsk University of Physical Education and Sport, Górski Str. 1, 80-336 Gdańsk, Poland. wieslaw.ziolkowski@awf.gda.pl.
6
Department of Cell Biology and Imaging, Institute of Zoology and Biomedical Research, Jagiellonian University, Gronostajowa 9, 30-387 Kraków, Poland. elzbieta.pyza@uj.edu.pl.
7
Department of Dermatology, University of Münster, Von-Esmarch-Str. 58, 48149 Münster, Germany. thomas.luger@ukmuenster.de.
8
Department of Cellular and Structural Biology, UT Health Science Center, San Antonio, TX 78229, USA. reiter@uthscsa.edu.
9
Department of Dermatology, University of Münster, Von-Esmarch-Str. 58, 48149 Münster, Germany. bohmm@uni-muenster.de.
10
Department of Dermatology, Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL 35294, USA. aslominski@uabmc.edu.
11
Pathology and Laboratory Medicine Service, VA Medical Center, Birmingham, AL 35249, USA. aslominski@uabmc.edu.

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

PMID:
30487387
PMCID:
PMC6320988
DOI:
10.3390/ijms19123786
[Indexed for MEDLINE]
Free PMC Article

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