Constitutive and UV‐induced metabolism of melatonin in keratinocytes and cell‐free systems

Abstract

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.

Dissecting the Impact of Chemotherapy on the Human Hair Follicle

“…28,79 Furthermore, acrolein decreases mitochondrial enzyme activities (mitochondrial complexes I, II, and III; superoxide dismutase; and glutathione peroxidase). 80 Our results furthermore encourage one to explore the chemotherapy-protective effects of antioxidants (ie, vitamin E, ␤-carotene, and melatonin) 69,81,82 that have been shown to protect from reactive oxygen species-induced mitochondrial DNA damage to protect selectively human scalp HFs (eg, after topical application in HF-targeting liposomes [83][84][85][86] from chemotherapy-induced oxidative and structural mitochondrial and nuclear DNA damage).…”

Long-term melatonin administration attenuates low-LET γ-radiation-induced lymphatic tissue injury during the reproductively active and inactive phases of Indian palm squirrels (Funambulus pennanti)

“…The effects of melatonin on the levels of a number of biochemical variables, on hormones and on oxidative and antioxidative status in mammals, and how they change in relation to their circadian patterns, have been reported [47,48]. Besides being a circadian and seasonal biorhythm regulator, a wide spectrum of targets and effects of melatonin has evolved in a variety of tissues, such as the gut, cerebrospinal fluid, ovary, skin, bone marrow, bile fluid and lymphocytes, as well as in whole organisms [49][50][51][52][53][54][55]. Antioxidant enzyme activities have been shown to exhibit circadian rhythms corresponding to melatonin rhythmicity and total antioxidant status in chicken brain, liver and lung [56].…”

Oncostatic effects of the indole melatonin and expression of its cytosolic and nuclear receptors in cultured human melanoma cell lines

“…Increasing evidence in the field suggests that melatonin acts at many extrapineal sites such as the gastrointestinal tract (11,12), the blood cell system (13), the retina (14), the bone marrow (15,16) and the skin (17)(18)(19)(20)(21)(22). In the epidermal keratinocytes, a constitutive and UV-induced melatonin metabolism has recently been described (23). Under physiologic conditions, melatonin participates in the regulation of keratinocyte proliferation (24)(25)(26), hair growth (26)(27)(28)(29)(30)(31) and melanogenesis (32,33).…”