Journal
JOURNAL OF PINEAL RESEARCH
Volume 54, Issue 3, Pages 303-312Publisher
WILEY
DOI: 10.1111/jpi.12018
Keywords
catalase; glutathione peroxidase; human full-thickness skin; 8-hydroxy-2 '-deoxyguanosine; melatonin; superoxide dismutase; ultraviolet radiation
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Funding
- Medical Faculty of the University of Lubeck, Germany
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UV radiation (UVR) induces serious structural and functional alterations in human skin leading to skin aging and carcinogenesis. Reactive oxygen species are key players in UVR-mediated photodamage and induce the DNA-base-oxidized, intermediate 8-hydroxy-2'-deoxyguanosine (8-OHdG). Herein, we report the protective action of melatonin against UVR-induced 8-OHdG formation and depletion of antioxidative enzymes using ex vivo human full-thickness skin exposed to UVR in a dose (0, 100, 300mJ/cm2)- and time-dependent manner (0, 24, 48hr post-UVR). Dynamics of depletion of antioxidative enzymes including catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD), or 8-OHdG formation were studied by real-time PCR and immunofluorescence/immunohistochemical staining. UVR-treated skin revealed significant and immediate (0hr 300mJ/cm2) reduction of gene expression, and this effect intensified within 24hr post-UVR. Simultaneous increase in 8-OHdG-positive keratinocytes occurred already after 0hr post-UVR reaching 71% and 99% up-regulation at 100 and 300mJ/cm2, respectively (P<0.001). Preincubation with melatonin (103m) led to 32% and 29% significant reductions in 8-OHdG-positive cells and the prevention of antioxidative enzyme gene and protein suppression. Thus, melatonin was shown to play a crucial role as a potent antioxidant and DNA protectant against UVR-induced oxidative damage in human skin.
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