Nrf2 Negatively Regulates Melanogenesis by Modulating PI3K/Akt Signaling |
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| Authors: | Jung-Min Shin Mi Yoon Kim Kyung-Cheol Sohn So-Young Jung Hae-Eul Lee Jae Woo Lim Sooil Kim Young-Ho Lee Myung Im Young-Joon Seo Chang Deok Kim Jeung-Hoon Lee Young Lee Tae-Jin Yoon |
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| Institution: | 1. Department of Dermatology and Research Institute for Medical Sciences, School of Medicine, Chungnam National University, Daejeon, Korea.; 2. Department of Anatomy, School of Medicine, Chungnam National University, Daejeon, Korea.; 3. Department of Dermatology and Institute of Health Sciences, School of Medicine, Gyeongsang National University, Jinju, Korea.; University of Texas Health Science Center at Houston, United States of America, |
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| Abstract: | Nrf2 plays a role in protection of cells against oxidative stress and xenobiotic damage by regulating cytoprotective genes. In this study, we investigated the effect of Nrf2 on melanogenesis in normal human melanocytes (NHMCs). When NHMCs were transduced with a recombinant adenovirus expressing Nrf2, melanin synthesis was significantly decreased. Consistent with this result, overexpression of Nrf2 decreased the expression of tyrosinase and tyrosinase-related protein 1. The inhibitory effect of Nrf2 was reversed by overexpression of Keap1, an intracellular regulator of Nrf2. Interestingly, Nrf2 overexpression resulted in marked activation of PI3K/Akt signaling. Conversely, inhibition of PI3K activity by treatment with wortmannin reversed the depigmentary effects of Nrf2. Taken together, these results strongly suggest that Nrf2 negatively regulates melanogenesis by modulating the PI3K/Akt signaling pathway. |
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