Nrf2 Negatively Regulates Melanogenesis by Modulating PI3K/Akt Signaling

被引：55
|
作者：
Shin, Jung-Min [1 ,2 ]
Kim, Mi Yoon [1 ,2 ]
Sohn, Kyung-Cheol [1 ,2 ]
Jung, So-Young [1 ,2 ]
Lee, Hae-Eul [1 ,2 ]
Lim, Jae Woo [1 ,2 ]
Kim, Sooil [3 ]
Lee, Young-Ho [3 ]
Im, Myung [1 ,2 ]
Seo, Young-Joon [1 ,2 ]
Kim, Chang Deok [1 ,2 ]
Lee, Jeung-Hoon [1 ,2 ]
Lee, Young [1 ,2 ]
Yoon, Tae-Jin [4 ,5 ]
机构：
[1] Chungnam Natl Univ, Sch Med, Dept Dermatol, Taejon, South Korea
[2] Chungnam Natl Univ, Sch Med, Res Inst Med Sci, Taejon, South Korea
[3] Chungnam Natl Univ, Sch Med, Dept Anat, Taejon, South Korea
[4] Gyeongsang Natl Univ, Sch Med, Dept Dermatol, Jinju, South Korea
[5] Gyeongsang Natl Univ, Sch Med, Inst Hlth Sci, Jinju, South Korea
来源：
PLOS ONE | 2014年 / 9卷 / 04期
关键词：
GENE-EXPRESSION; PROTEASOMAL DEGRADATION; TRANSCRIPTION FACTOR; MELANOMA-CELLS; ENZYME GENES; PATHWAY; PIGMENTATION; KERATINOCYTES; ACTIVATION; TYROSINASE;
D O I：
10.1371/journal.pone.0096035
中图分类号：
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号：
07 ; 0710 ; 09 ;
摘要：
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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页数：7
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