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.
J Pineal Res
; 54(3): 303-12, 2013 Apr.
Article
em En
| MEDLINE
| ID: mdl-23110400
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fenômenos Fisiológicos da Pele
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Dano ao DNA
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Desoxiguanosina
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Melatonina
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Antioxidantes
Limite:
Adult
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Humans
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Middle aged
Idioma:
En
Revista:
J Pineal Res
Assunto da revista:
ENDOCRINOLOGIA
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Alemanha