TY - JOUR
T1 - Melatonin and its metabolites ameliorate UVR-induced mitochondrial oxidative stress in human MNT-1 melanoma cells
AU - Kleszczyński, Konrad
AU - Bilska, Bernadetta
AU - Stegemann, Agatha
AU - Flis, Damian Jozef
AU - Ziolkowski, Wieslaw
AU - Pyza, Elżbieta
AU - Luger, Thomas A.
AU - Reiter, Russel J.
AU - Böhm, Markus
AU - Slominski, Andrzej T.
N1 - Publisher Copyright:
© 2018 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2018/12
Y1 - 2018/12
N2 - 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.
AB - 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.
KW - Calcium homeostasis
KW - Catalase
KW - Melanoma cells
KW - Metabolites of melatonin
KW - Mitochondria
KW - Oxidative phosphorylation
KW - Ultraviolet radiation
UR - https://www.scopus.com/pages/publications/85057537957
UR - https://www.scopus.com/pages/publications/85057537957#tab=citedBy
U2 - 10.3390/ijms19123786
DO - 10.3390/ijms19123786
M3 - Article
C2 - 30487387
AN - SCOPUS:85057537957
SN - 1661-6596
VL - 19
JO - International journal of molecular sciences
JF - International journal of molecular sciences
IS - 12
M1 - 3786
ER -