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

Ultraviolet light (UV) radiation causes skin-tanning, which is thought to b e mediated by stimulating the release of melanogenic factors from keratinoc ytes as well as other cells, Nitric oxide (NO) has been reported to be gene rated after UV radiation and to stimulate melanocytes as one of the melanog ens. In a previous experiment by another group on melanogenesis induced by NO, increases in both tyrosinase activity and tyrosinase protein levels wer e 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-ind uced melanogenesis, Tyrosinase mRNA expression was found to be induced 2 hr after a single treatment with S-nitroso-N-acetyl-L-arginine. An increase o f tyrosinase activity was also detected time-dependently within the 24-hr p eriod, accompanied by an increase of tyrosinase protein levels, The inducti on of mRNA expression was suppressed by a cyclic guanosine 3',5'-monophosph ate (cGMP)-dependent protein kinase (cGMP/PKG) inhibitor. These results sug gest that the enhancement of tyrosinase gene expression via the cGMP pathwa y may be a primary mechanism for NO-induced melanogenesis.