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

Pigment Cell Melanoma Res. 2009 Dec;22(6):809-18. doi: 10.1111/j.1755-148X.2009.00615.x. Epub 2009 Jul 29.


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 damage, which partially explain the strong association of loss-of-function MC1R with melanoma.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 8-Hydroxy-2'-Deoxyguanosine
  • Agouti Signaling Protein / metabolism
  • Antioxidants / metabolism
  • Catalase / metabolism
  • Cells, Cultured
  • DNA Damage
  • Deoxyguanosine / analogs & derivatives
  • Deoxyguanosine / metabolism
  • Dose-Response Relationship, Radiation
  • Ferritins / metabolism
  • Hormones / pharmacology
  • Humans
  • Hydrogen Peroxide / metabolism
  • Melanocytes / cytology
  • Melanocytes / drug effects
  • Melanocytes / metabolism*
  • Melanocytes / radiation effects*
  • Oxidants / metabolism
  • Oxidative Stress*
  • Ultraviolet Rays*
  • alpha-MSH / genetics
  • alpha-MSH / metabolism*
  • alpha-MSH / pharmacology


  • Agouti Signaling Protein
  • Antioxidants
  • Hormones
  • Oxidants
  • alpha-MSH
  • 8-Hydroxy-2'-Deoxyguanosine
  • Ferritins
  • Hydrogen Peroxide
  • Catalase
  • Deoxyguanosine