Abstract

Ultraviolet B (UVB) radiation is the main physiological stimulus for human skin pigmentation; however, the molecular mechanisms underlying this process are still unclear. Recently, nitric oxide (NO) and cGMP have been involved in mediation of skin erythema induced by UVB. Therefore, we investigated the role of NO and cGMP in UVB-induced melanogenesis. In this study, we demonstrated that UVB stimulation of melanogenesis was mimicked by exogenous NO donors. Additionally, we showed that NO stimulated cGMP synthesis and that cGMP was also a potent stimulator of melanogenesis. Furthermore, the inhibition of the melanogenic effect of NO by guanylate cyclase inhibitor demonstrated that NO mediated its effect through the activation of guanylyl cyclase. Interestingly, 1 min after UVB irradiation, we observed a significant increase in cGMP content in melanocytes. The effects of UVB on cGMP production and on melanogenesis were blocked by both guanylate cyclase and NO synthase inhibitors. Additionally, inhibition of cGMP-dependent kinase also prevented the stimulation of melanogenesis by UVB and NO. Therefore, we concluded that NO and cGMP production is required for UVB-induced melanogenesis and that cGMP mediated its melanogenic effects mainly through the activation of cGMP-dependent kinase.

Highlights

  • Epidermal melanin is responsible for skin darkening and is synthesized by melanocytes as the result of a cascade of enzymatic reactions

  • In this study we show that stimulation of melanogenesis depends on a linear transduction pathway involving Ultraviolet B (UVB), nitric oxide (NO), and cGMP

  • We clearly demonstrate that NO is a potent stimulator of tyrosinase activity and melanin synthesis

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Summary

EXPERIMENTAL PROCEDURES

L-NMA, SNAP, and carboxy-PTIO were from Affiniti (Nottingham, United Kingdom). Ly 83583, KT 5823, and NOR-4 were from Calbiochem. DEA-NO was from Cayman chemicals (Ann Arbor, Mi). The cGMP enzyme immunoassay system was from Amersham Corp. All other products used for cell culture and biochemical analysis were obtained as previously reported [14]

Cell Culture
NO Donor Treatment
Ultraviolet Irradiation
Melanogenic Activity Assays
Cyclic GMP Determination
RESULTS
DISCUSSION
Full Text
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