PLoS ONE (Jan 2014)

Nrf2 negatively regulates melanogenesis by modulating PI3K/Akt signaling.

  • 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

DOI
https://doi.org/10.1371/journal.pone.0096035
Journal volume & issue
Vol. 9, no. 4
p. e96035

Abstract

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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.