Nrf2 negatively regulates melanogenesis by modulating PI3K/Akt signaling.
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.
Department of Dermatology and Research Institute for Medical Sciences, School of Medicine, Chungnam National University, Daejeon, Korea.
Jung-Min
JM
Shin
Department of Dermatology and Research Institute for Medical Sciences, School of Medicine, Chungnam National University, Daejeon, Korea.
Mi Yoon
MY
Kim
Department of Dermatology and Research Institute for Medical Sciences, School of Medicine, Chungnam National University, Daejeon, Korea.
Kyung-Cheol
KC
Sohn
Department of Dermatology and Research Institute for Medical Sciences, School of Medicine, Chungnam National University, Daejeon, Korea.
So-Young
SY
Jung
Department of Dermatology and Research Institute for Medical Sciences, School of Medicine, Chungnam National University, Daejeon, Korea.
Hae-Eul
HE
Lee
Department of Dermatology and Research Institute for Medical Sciences, School of Medicine, Chungnam National University, Daejeon, Korea.
Jae Woo
JW
Lim
Department of Anatomy, School of Medicine, Chungnam National University, Daejeon, Korea.
Sooil
S
Kim
Department of Anatomy, School of Medicine, Chungnam National University, Daejeon, Korea.
Young-Ho
YH
Lee
Department of Dermatology and Research Institute for Medical Sciences, School of Medicine, Chungnam National University, Daejeon, Korea.
Myung
M
Im
Department of Dermatology and Research Institute for Medical Sciences, School of Medicine, Chungnam National University, Daejeon, Korea.
Young-Joon
YJ
Seo
Department of Dermatology and Research Institute for Medical Sciences, School of Medicine, Chungnam National University, Daejeon, Korea.
Chang Deok
CD
Kim
Department of Dermatology and Research Institute for Medical Sciences, School of Medicine, Chungnam National University, Daejeon, Korea.
Jeung-Hoon
JH
Lee
Department of Dermatology and Research Institute for Medical Sciences, School of Medicine, Chungnam National University, Daejeon, Korea.
Young
Y
Lee
Department of Dermatology and Institute of Health Sciences, School of Medicine, Gyeongsang National University, Jinju, Korea.
Tae-Jin
TJ
Yoon
D000256:Adenoviridae / Q000235:genetics; D000730:Androstadienes / Q000494:pharmacology; D002478:Cells, Cultured; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D000072019:Kelch-Like ECH-Associated Protein 1; D008543:Melanins / Q000378:metabolism*; D008544:Melanocytes / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism; D014442:Monophenol Monooxygenase / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism*; D051058:Oncogene Protein v-akt / Q000378:metabolism*; D010088:Oxidoreductases / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D015398:Signal Transduction; D012880:Skin Pigmentation; D014161:Transduction, Genetic; D000077191:Wortmannin
D000730:Androstadienes; D047908:Intracellular Signaling Peptides and Proteins; C431364:KEAP1 protein, human; D000072019:Kelch-Like ECH-Associated Protein 1; D008543:Melanins; D008562:Membrane Glycoproteins; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D047428:Protein Kinase Inhibitors; D010088:Oxidoreductases; C489799:TYRP1 protein, human; D014442:Monophenol Monooxygenase; D019869:Phosphatidylinositol 3-Kinases; D051058:Oncogene Protein v-akt; D000077191:Wortmannin