期刊
JOURNAL OF PINEAL RESEARCH
卷 54, 期 3, 页码 303-312出版社
WILEY
DOI: 10.1111/jpi.12018
关键词
catalase; glutathione peroxidase; human full-thickness skin; 8-hydroxy-2 '-deoxyguanosine; melatonin; superoxide dismutase; ultraviolet radiation
资金
- Medical Faculty of the University of Lubeck, Germany
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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