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

Xiuzu Song1, Nicole Mosby, Jennifer Yang

  • 1Department of Dermatology, University of Cincinnati College of Medicine, Cincinnati, OH, USA.

Pigment Cell & Melanoma Research
|August 8, 2009
PubMed

Insights

Ultraviolet radiation (UV) causes oxidative DNA damage in melanocytes. Alpha-melanocortin (alpha-MSH) protects against this UV-induced damage by increasing antioxidant enzymes like catalase, mediated through the melanocortin 1 receptor (MC1R).

Area of Science:

  • Dermatology
  • Molecular Biology
  • Genetics

Background:

  • Ultraviolet (UV) radiation exposure is a known carcinogen, primarily causing DNA damage in skin cells.
  • UV-signature mutations are infrequent in melanoma, suggesting alternative DNA damage pathways like oxidative stress may be involved in melanocyte transformation.
  • Hydrogen peroxide generation and decreased catalase activity are observed in UV-irradiated melanocytes.

Purpose of the Study:

  • To investigate the role of oxidative DNA damage in UV-irradiated human melanocytes.
  • To determine the protective effects of alpha-melanocortin (alpha-MSH) against UV-induced oxidative DNA damage.
  • To elucidate the molecular mechanisms underlying alpha-MSH's protective role, including the involvement of the melanocortin 1 receptor (MC1R).

Main Methods:

  • Cultured human melanocytes were exposed to UV radiation.
  • Hydrogen peroxide generation and 7,8-dihydro-8-oxyguanine (8-oxodG) levels were measured.
  • Catalase activity and protein levels were assessed.
  • Melanocytes were pretreated with alpha-MSH, and the effects were evaluated in cells with functional or non-functional MC1R, with or without agouti signaling protein (ASIP) analog treatment.

Main Results:

  • UV irradiation caused immediate, dose-dependent hydrogen peroxide generation and decreased catalase activity in melanocytes.
  • Pretreatment with alpha-MSH significantly reduced UV-induced 8-oxodG formation, a marker of oxidative DNA damage.
  • Alpha-MSH increased protein levels of catalase and ferritin.
  • The protective effect of alpha-MSH was dependent on MC1R activation and was blocked by ASIP-YY.

Conclusions:

  • UV radiation induces significant oxidative DNA damage in human melanocytes.
  • Alpha-melanocortin (alpha-MSH) effectively reduces UV-induced oxidative DNA damage through MC1R activation.
  • These findings highlight a mechanism by which alpha-MSH protects melanocytes, potentially explaining the link between MC1R variants and melanoma risk.

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