Aug 8, 2009

alpha-MSH activates immediate defense responses to UV-induced oxidative stress in human melanocytes

Pigment Cell & Melanoma Research
Xiuzu SongAna L Kadekaro

Abstract

Exposure of cultured human melanocytes to ultraviolet radiation (UV) results in DNA damage. In melanoma, UV-signature mutations resulting from unrepaired photoproducts are rare, suggesting the possible involvement of oxidative DNA damage in melanocyte malignant transformation. Here we present data demonstrating immediate dose-dependent generation of hydrogen peroxide in UV-irradiated melanocytes, which correlated directly with a decrease in catalase activity. Pretreatment of melanocytes with alpha-melanocortin (alpha-MSH) reduced the UV-induced generation of 7,8-dihydro-8-oxyguanine (8-oxodG), a major form of oxidative DNA damage. Pretreatment with alpha-MSH also increased the protein levels of catalase and ferritin. The effect of alpha-MSH on 8-oxodG induction was mediated by activation of the melanocortin 1 receptor (MC1R), as it was absent in melanocytes expressing loss-of-function MC1R, and blocked by concomitant treatment with an analog of agouti signaling protein (ASIP), ASIP-YY. This study provides unequivocal evidence for induction of oxidative DNA damage by UV in human melanocytes and reduction of this damage by alpha-MSH. Our data unravel some mechanisms by which alpha-MSH protects melanocytes from oxidative DNA damag...Continue Reading

  • References66
  • Citations30

References

Mentioned in this Paper

Melanocyte
Protein Measurement
Hydrogen Peroxide
8-oxyguanine
ACTH (1-13)NH2
MC1R Protein
Antioxidant Effect
Oxidative Stress
Oxidative Stress Analysis
Melanoma vaccine

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