Ultraviolet Radiation-Induced Mitochondrial Disturbances Are Attenuated by Metabolites of Melatonin in Human Epidermal Keratinocytes
Chantal E. Holtkamp,
Dawid Warmus,
Klaudia Bonowicz,
Maciej Gagat,
Kinga Linowiecka,
Agnieszka Wolnicka-Glubisz,
Russel J. Reiter,
Markus Böhm,
Andrzej T. Slominski,
Kerstin Steinbrink,
Konrad Kleszczyński
Affiliations
Chantal E. Holtkamp
Department of Dermatology, University of Münster, Von-Esmarch-Str. 58, 48149 Münster, Germany
Dawid Warmus
Department of Biophysics and Cancer Biology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Gronostajowa 7, 30-387 Krakow, Poland
Klaudia Bonowicz
Department of Histology and Embryology, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, 85-092 Bydgoszcz, Poland
Maciej Gagat
Department of Histology and Embryology, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, 85-092 Bydgoszcz, Poland
Kinga Linowiecka
Department of Human Biology, Faculty of Biological and Veterinary Sciences, Nicolaus Copernicus University, Lwowska 1, 87-100 Toruń, Poland
Agnieszka Wolnicka-Glubisz
Department of Biophysics and Cancer Biology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Gronostajowa 7, 30-387 Krakow, Poland
Russel J. Reiter
Department of Cell Systems and Anatomy, UT Health, Long School of Medicine, San Antonio, TX 78229, USA
Markus Böhm
Department of Dermatology, University of Münster, Von-Esmarch-Str. 58, 48149 Münster, Germany
Andrzej T. Slominski
Department of Dermatology, Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL 35294, USA
Kerstin Steinbrink
Department of Dermatology, University of Münster, Von-Esmarch-Str. 58, 48149 Münster, Germany
Konrad Kleszczyński
Department of Dermatology, University of Münster, Von-Esmarch-Str. 58, 48149 Münster, Germany
Melatonin (N-acetyl-5-methoxytryptamine) is recognized as an effective antioxidant produced by the pineal gland, brain and peripheral organs, which also has anti-inflammatory, immunomodulatory, and anti-tumour capacities. Melatonin has been reported as a substance that counteracts ultraviolet radiation B (UVB)-induced intracellular disturbances. Nevertheless, the mechanistic actions of related molecules including its kynurenic derivatives (N1-acetyl-N2-formyl-5-methoxykynurenine (AFMK)), its indolic derivatives (6-hydroxymelatonin (6(OH)MEL) and 5-methoxytryptamine (5-MT)) and its precursor N-acetylserotonin (NAS) are only poorly understood. Herein, we treated human epidermal keratinocytes with UVB and assessed the protective effect of the studied substances in terms of the maintenance of mitochondrial function or their radical scavenging capacity. Our results show that UVB caused the significant elevation of catalase (CAT) and superoxide dismutase (Mn-SOD), the dissipation of mitochondrial transmembrane potential (mtΔΨ), a reduction in ATP synthesis, and the enhanced release of cytochrome c into cytosol, leading subsequently to UVB-mediated activation of the caspases and apoptosis (appearance of sub-G1 population). Our findings, combined with data reported so far, indicate the counteracting and beneficial actions of melatonin and its molecular derivatives against these deleterious changes within mitochondria. Therefore, they define a path to the development of novel strategies delaying mitochondrial aging and promoting the well-being of human skin.
