H₂O₂ promotes the aging process of melanogenesis through modulation of MITF and Nrf2

The purpose of this study is to investigate the effect of H₂O₂ on the aging of melanogenesis in human melanocytes. The staining of SA-β-galactosidase, an aging marker, was remarkably increased in the cells aged with H₂O₂ at 62.5 µM or more compared with young cells. The intracellular H₂O₂ level and melanin synthesis were also reduced in both H₂O₂-treated cells and senescent cells compared with young cells in DCFH-DA assay. Both the senescent cells and the H₂O₂-treated cells showed higher expression level of Catalase than young cells in western blot and immunofluorescence staining. Furthermore, the expression levels of TRP-1, TRP-2 and p300 were reduced in both senescent cells and the H₂O₂-treated cells, but that of SIRT-1 was inverted compared with young cells. In addition, H₂O₂ reduced the expression level of MITF but increased that of Nrf2 in nucleus. Those results indicate that the expression levels of antioxidant enzymes in senescent cells and H₂O₂-treated cell are upregulated, but the expression levels of proteins involved in melanin synthesis are downregulated. Above findings suggest that H₂O₂ could play a key role in the aging process of melanogenesis through modulation of MITF and Nrf2.