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.
KeywordsMelanocytes Aging H2O2 MITF SIRT-1 P300
This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (No.2017R1D1A3B06028000).
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
Ethical approval and informed consent not required for the paper.
- 2.Joshi PG, Nair N, Begum G, Joshi NB, Sinkar VP, Vora S (2007) Melanocyte–keratinocyte interaction induces calcium signalling and melanin transfer to keratinocytes. Pigment Cell Melanoma Res 20(5):380–384Google Scholar
- 3.Arck PC, Overall R, Spatz K, Liezman C, Handjiski B, Klapp BF, Birch-Machin MA, Peters EMJ (2006) Towards a “free radical theory of graying”: melanocyte apoptosis in the aging human hair follicle is an indicator of oxidative stress induced tissue damage. FASEB J 20(9):1567–1569CrossRefGoogle Scholar
- 4.Nakeenopakun Y, Chaiyawatthanananth P, Itharat A (2017) Determination of free radical protective activity from hydrogen peroxide, antioxidant and melanogenesis stimulating activities of Eclipta prostrate Linn. and Sapindus rarak DC. for Hair Dye Product. J Med Assoc Thail 100(6):192Google Scholar
- 8.Jian Z, Li K, Song P, Zhu G, Zhu L, Cui T, Liu B, Tang L, Wang X, Wang G (2014) Impaired activation of the Nrf2-ARE signaling pathway undermines H2O2-induced oxidative stress response: a possible mechanism for melanocyte degeneration in vitiligo. J Invest Dermatol 134(8):2221–2230CrossRefGoogle Scholar
- 10.Haslam IS, Jadkauskaite L, Szabó IL, Staege S, Hesebeck-Brinckmann J, Jenkins G, Bhogal RK, Lim F-L, Farjo N, Farjo B (2017) Oxidative damage control in a human (mini-) organ: Nrf2 activation protects against oxidative stress-induced hair growth inhibition. J Invest Dermatol 137(2):295–304CrossRefGoogle Scholar
- 15.Yang S-G, Wang W-Y, Ling T-J, Feng Y, Du X-T, Zhang X, Sun X-X, Zhao M, Xue D, Yang Y (2010) Alpha-tocopherol quinone inhibits beta-amyloid aggregation and cytotoxicity, disaggregates preformed fibrils and decreases the production of reactive oxygen species, NO and inflammatory cytokines. Neurochem Int 57(8):914–922CrossRefGoogle Scholar
- 21.Diraviyam T, Radhakrishnan M, Balagurunathan R (2011) Antioxidant activity of melanin pigment from Streptomyces species D5 isolated from Desert soil, Rajasthan, India. Drug Invent Today 3(3):12–13Google Scholar
- 25.Bandyopadhyay D, Okan NA, Bales E, Nascimento L, Cole PA, Medrano EE (2002) Down-regulation of p300/CBP histone acetyltransferase activates a senescence checkpoint in human melanocytes. Cancer Res 62(21):6231–6239Google Scholar