Constitutive and UV-induced metabolism of melatonin in keratinocytes and cell-free systems.
Melatonin, which can be produced in the skin, exerts a protective effect against damage induced by UV radiation (UVR). We have investigated the effect of UVB, the most damaging component of UVR, on melatonin metabolism in HaCaT keratinocytes and in a cell-free system. Four metabolites were identified by HPLC and LC-MS: 6-hydroxymelatonin, N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK), 2-hydroxymelatonin (the main intermediate between melatonin and AFMK), and 4-hydroxymelatonin. Concentrations of these photoproducts were directly proportional to UVR-dose and to melatonin substrate content, and their accumulation was time-dependent. The UVR-dependent increase of AFMK and 2-hydroxymelatonin was also detected in keratinocytes, where it was accompanied by simultaneous consumption of intracellular melatonin. Of note, melatonin and its two major metabolites, 2-hydroxymelatonin and AFMK, were also detected in untreated keratinocytes, neither irradiated nor preincubated with melatonin. Thus, intracellular melatonin metabolism is enhanced under exposure to UVR. The additional biological activity of these individual melatonin metabolites increases the spectrum of potential actions of the recently identified cutaneous melatoninergic system.
Fischer
Tobias W
TW
Department of Patholology and Laboratory Medicine, University of Tennessee Health Science Center, 930 Madison Ave., Memphis, Tennessee 38163, USA.
Sweatman
Trevor W
TW
Semak
Igor
I
Sayre
Robert M
RM
Wortsman
Jacobo
J
Slominski
Andrzej
A
D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001692:Biological Transport / Q000528:radiation effects; D002460:Cell Line; D002474:Cell-Free System; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects*; D008550:Melatonin / Q000378:metabolism* / Q000528:radiation effects; D014466:Ultraviolet Rays
D000900:Anti-Bacterial Agents; D008550:Melatonin