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Constitutive and UV‐induced metabolism of melatonin in keratinocytes and cell‐free systems
Author(s) -
Fischer Tobias W.,
Sweatman Trevor W.,
Semak Igor,
Sayre Robert M.,
Wortsman Jacobo,
Slominski Andrƶej
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.05-5227fje
Subject(s) - melatonin , hacat , intracellular , metabolism , photoprotection , biology , endogeny , chemistry , biochemistry , in vitro , endocrinology , photosynthesis
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, N 1 ‐acetyl‐N 2 ‐formy1–5‐methoxykynuramine (AFMK), 2‐hydroxymela‐tonin (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‐de‐pendent 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, T. W., Sweatman, T. W., Semak, L., Sayre, R. M., Wortsman, J., Slominski, A. Constitutive and UV‐induced metabolism of melatonin in keratinocytes and cell‐free systems. FASEB J. 20, E897–E907 (2006)