title: Melatonin enhances antioxidative enzyme gene expression (CAT, GPx, SOD), prevents their UVR-induced depletion, and protects against the formation of DNA damage (8-hydroxy-2'-deoxyguanosine) in ex vivo human skin.
abstract: 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, 300 mJ/cm(2))- and time-dependent manner (0, 24, 48 hr 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 (0 hr 300 mJ/cm(2)) reduction of gene expression, and this effect intensified within 24 hr post-UVR. Simultaneous increase in 8-OHdG-positive keratinocytes occurred already after 0 hr post-UVR reaching 71% and 99% up-regulation at 100 and 300 mJ/cm(2), respectively (P < 0.001). Preincubation with melatonin (10(-3) M) 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.
authors.affiliation: Department of Dermatology, Allergology and Venerology, University of Lübeck, Lübeck, Germany. Tobias.Fischer@uk-sh.de
authors.forename: Tobias W
authors.initials: TW
authors.lastname: Fischer
authors.forename: Konrad
authors.initials: K
authors.lastname: Kleszczyński
authors.forename: Lena H
authors.initials: LH
authors.lastname: Hardkop
authors.forename: Nathalie
authors.initials: N
authors.lastname: Kruse
authors.forename: Detlef
authors.initials: D
authors.lastname: Zillikens
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000328:Adult; D000704:Analysis of Variance; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology*; D002374:Catalase / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008550:Melatonin / Q000494:pharmacology*; D008875:Middle Aged; D009924:Organ Culture Techniques; D060888:Real-Time Polymerase Chain Reaction; D012867:Skin / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism / Q000528:radiation effects; D012879:Skin Physiological Phenomena / Q000187:drug effects*; D013482:Superoxide Dismutase / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D014466:Ultraviolet Rays; D055815:Young Adult
chemical_list: D000975:Antioxidants; D000080242:8-Hydroxy-2'-Deoxyguanosine; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D003849:Deoxyguanosine; D008550:Melatonin