Cosmetics, Vol. 4, Pages 43: Degradation of Tyrosinase by Melanosomal pH Change and a New Mechanism of Whitening with Propylparaben

Cosmetics, Vol. 4, Pages 43: Degradation of Tyrosinase by Melanosomal pH Change and a New Mechanism of Whitening with Propylparaben

Cosmetics doi: 10.3390/cosmetics4040043

Authors: Haifeng Zeng Akane Harashima Koichi Kato Lihao Gu Yosuke Motomura Ryoichi Otsuka Kazuhisa Maeda

Many active cosmetic ingredients formulated as medicated whitening products (quasi-drugs) achieve their effect through inhibition of tyrosinase activity, but no products can achieve this effect through degradation of intramelanosomal tyrosinase. Melanin is synthesized by tyrosinase, which is localized to the membrane of melanosomes in melanocytes. It has been reported that the optimal pH of tyrosinase activity is nearly neutral and decreases under acidic conditions. The environment in melanosomes that tyrosinase acts on has attracted attention from researchers. We found that tyrosinase was degraded by acidification of melanosomes, thereby decreasing its activity. We found that both inhibitors of aspartic protease and cysteine protease decreased the degradation of tyrosinase. It is thought that aspartic protease and cysteine protease are participating in the degradation of tyrosinase in acid melanosome. Melanosomal pH is regulated by Na+/H+ exchangers and V-ATPase. We investigated the mechanisms of the inhibitory effect of melanin production of propylparaben using B16 melanoma cells. The expression level of mRNA of tyrosinase and related proteins (Trp-1 and Dct) was not affected by propylparaben; however, the protein levels in melanosomes decreased. We investigated the mechanisms of the inhibitory effect of propylparaben on melanin production using B16 melanoma cells. The effects of propylparaben on the mRNA expression of Na+/H+ exchangers and Na+/Ca2+ exchangers, as well as the melanosome pH levels were examined. Propylparaben decreased gene expression in both exchangers. It was confirmed that propylparaben decreased melanosomal pH by staining using an intracellular pH indicator. The results suggest that propylparaben down-regulated melanin production through acidification of melanosomes.

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