Up-regulation of tyrosinase gene by nitric oxide in human melanocytes

Pigment Cell Res. 2000 Aug;13(4):248-52. doi: 10.1034/j.1600-0749.2000.130406.x.


Ultraviolet light (UV) radiation causes skin-tanning, which is thought to be mediated by stimulating the release of melanogenic factors from keratinocytes as well as other cells. Nitric oxide (NO) has been reported to be generated after UV radiation and to stimulate melanocytes as one of the melanogens. In a previous experiment by another group on melanogenesis induced by NO, increases in both tyrosinase activity and tyrosinase protein levels were observed after daily stimulation of NO for 4 days. In the present study, we investigated tyrosinase gene expression within the first 24 hr of NO-induced melanogenesis. Tyrosinase mRNA expression was found to be induced 2 hr after a single treatment with S-nitroso-N-acetyl-L-arginine. An increase of tyrosinase activity was also detected time-dependently within the 24-hr period, accompanied by an increase of tyrosinase protein levels. The induction of mRNA expression was suppressed by a cyclic guanosine 3',5'-monophosphate (cGMP)-dependent protein kinase (cGMP/PKG) inhibitor. These results suggest that the enhancement of tyrosinase gene expression via the cGMP pathway may be a primary mechanism for NO-induced melanogenesis.

MeSH terms

  • Alkaloids / pharmacology
  • Carbazoles*
  • Cells, Cultured
  • Cyclic GMP / metabolism
  • Cyclic GMP-Dependent Protein Kinases / antagonists & inhibitors
  • Cyclic GMP-Dependent Protein Kinases / metabolism
  • Enzyme Inhibitors / pharmacology
  • Gene Expression Regulation, Enzymologic / drug effects
  • Humans
  • Indoles*
  • Melanocytes / drug effects
  • Melanocytes / enzymology*
  • Monophenol Monooxygenase / genetics*
  • Monophenol Monooxygenase / metabolism
  • Nitric Oxide / metabolism
  • Nitric Oxide / pharmacology*
  • Penicillamine / analogs & derivatives*
  • Penicillamine / pharmacology
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • S-Nitroso-N-Acetylpenicillamine
  • Tyrosine 3-Monooxygenase / metabolism
  • Up-Regulation / drug effects


  • Alkaloids
  • Carbazoles
  • Enzyme Inhibitors
  • Indoles
  • RNA, Messenger
  • KT 5823
  • Nitric Oxide
  • S-Nitroso-N-Acetylpenicillamine
  • Tyrosine 3-Monooxygenase
  • Monophenol Monooxygenase
  • Cyclic GMP-Dependent Protein Kinases
  • Penicillamine
  • Cyclic GMP