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...

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Bibliographic Details
Published in:PloS one 2014-04, Vol.9 (4), p.e96035-e96035
Main Authors: Shin, Jung-Min, Kim, Mi Yoon, Sohn, Kyung-Cheol, Jung, So-Young, Lee, Hae-Eul, Lim, Jae Woo, Kim, Sooil, Lee, Young-Ho, Im, Myung, Seo, Young-Joon, Kim, Chang Deok, Lee, Jeung-Hoon, Lee, Young, Yoon, Tae-Jin
Format: Article
Language:English
Subjects:
1-Phosphatidylinositol 3-kinase
Adenoviridae - genetics
Adenoviruses
AKT protein
Analysis
Androstadienes - pharmacology
Antioxidants
Biology and life sciences
Cell cycle
Cells, Cultured
Dermatology
Distribution
Enzymes
Fibroblasts
Gene expression
Homeostasis
Humans
Intracellular Signaling Peptides and Proteins - metabolism
Kelch-Like ECH-Associated Protein 1
Kinases
Medicine
Medicine and Health Sciences
Melanin
Melanins - metabolism
Melanocytes
Melanocytes - metabolism
Melanoma
Membrane Glycoproteins - metabolism
Monophenol Monooxygenase - metabolism
NF-E2-Related Factor 2 - genetics
NF-E2-Related Factor 2 - metabolism
Oncogene Protein v-akt - metabolism
Oxidative stress
Oxidoreductases - metabolism
Phosphatidylinositol 3-Kinases - metabolism
Protein Kinase Inhibitors - pharmacology
Proteins
Rodents
Signal Transduction
Signaling
Skin Pigmentation
Studies
Transcription factors
Transduction, Genetic
Tyrosinase
Tyrosinase-related protein 1
Vitiligo
Wortmannin
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Summary: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0096035