Fiche publication
Date publication
novembre 2018
Journal
Science signaling
Auteurs
Membres identifiés du Cancéropôle Est :
Dr NARDIN Charlée
Tous les auteurs :
Zhou D, Ota K, Nardin C, Feldman M, Widman A, Wind O, Simon A, Reilly M, Levin LR, Buck J, Wakamatsu K, Ito S, Zippin JH
Lien Pubmed
Résumé
The production of melanin increases skin pigmentation and reduces the risk of skin cancer. Melanin production depends on the pH of melanosomes, which are more acidic in lighter-skinned than in darker-skinned people. We showed that inhibition of soluble adenylyl cyclase (sAC) controlled pigmentation by increasing the pH of melanosomes both in cells and in vivo. Distinct from the canonical melanocortin 1 receptor (MC1R)-dependent cAMP pathway that controls pigmentation by altering gene expression, we found that inhibition of sAC increased pigmentation by increasing the activity of tyrosinase, the rate-limiting enzyme in melanin synthesis, which is more active at basic pH. We demonstrated that the effect of sAC activity on pH and melanin production in human melanocytes depended on the skin color of the donor. Last, we identified sAC inhibitors as a new class of drugs that increase melanosome pH and pigmentation in vivo, suggesting that pharmacologic inhibition of this pathway may affect skin cancer risk or pigmentation conditions.
Mots clés
Adenylyl Cyclases, metabolism, Animals, Cyclic AMP, metabolism, Gene Deletion, Gene Expression Profiling, Humans, Hydrogen-Ion Concentration, Keratinocytes, metabolism, Melanins, metabolism, Melanocytes, cytology, Melanosomes, metabolism, Mice, Mice, Inbred C3H, Mice, Knockout, Monophenol Monooxygenase, metabolism, Pigmentation, Receptor, Melanocortin, Type 1, metabolism, Skin, metabolism, Skin Neoplasms, metabolism, Skin Pigmentation, Tanning
Référence
Sci Signal. 2018 11 6;11(555):
