Proton pump inhibitors decrease melanogenesis in melanocytes

Abstract

Proton pump inhibitors (PPIs) are widely used as inhibitors of gastric juice secretion for treatment of gastroesophageal reflux disease. However, there are no previous studies of the effects on melanogenesis resulting from PPI treatments. Therefore, the aim of the present study was to investigate the effects of PPIs on melanogenesis in melan-a cells derived from immortalized mouse melanocytes. Tyrosinase activity and copper-chelating activity were measured spectrophotometrically. In addition, the melanin content and viability of melan-a cells treated with PPIs were assessed and the mRNA levels of melanogenesis-associated genes were measured by reverse transcription-polymerase chain reaction. Treatment with rabeprazole, but not the other PPIs tested, resulted in strong, dose-dependent inhibition of mushroom tyrosinase (TYR). By contrast, each of the PPIs tested exhibited copper-chelating activity. Treatment of melan-a cells with 100 µM concentrations of the PPIs resulted in significantly reduced melanin synthesis and reduced expression of several melanogenesis-associated genes, including , TYR-related protein-1 () and , and microphthalmia-associated transcription factor, but did notresult in cytotoxic effects. These results suggest that PPIs inhibit melanin biosynthesis in melan-a cells via the downregulation of melanogenesis-associated genes. Furthermore, the findings indicate that PPIs in general could be utilized as skin-whitening agents and/or as biomaterial for treating hyperpigmentation disorders.

Melanogenesis Inhibitors

“…Omeprazole, a PPI used to treat gastroesophageal reflux disease, has been shown to inhibit melanogenesis by blocking ATP7A, which is a copper-transporting P-type ATPase that delivers copper to tyrosinase within the secretory pathway (59). Other PPIs, such as rabeprazole, lansoprazole, pantoprazole and esomeprazole, have also been found to inhibit melanogenesis via their copper-chelating activities without inducing cytotoxicity (60).…”

How to design robust assays for human skin pigmentation: A “Tortoise and Hare challenge”

“…Despite the sophistication and seduction of the ‐omics technology blizzard of recent years, there is good evidence that the electron‐stripped hydrogen atom can control pH within the melanosome. In this way, protons can regulate the catalytic activity of tyrosinase, 58–60 and thus pigmentation levels in the skin and hair follicle. While any reliable assay to determine the impact of an intervention to modulate human skin pigmentation should start at the proverbial square one, this is only the first step on the long journey to an optimal pigmentation phenotype.…”