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Galangin Activates the ERK/AKT-Driven Nrf2 Signaling Pathway to Increase the Level of Reduced Glutathione in Human Keratinocytes

  • Hewage, Susara Ruwan Kumara Madduma (School of Medicine and Institute for Nuclear Science and Technology, Jeju National University) ;
  • Piao, Mei Jing (School of Medicine and Institute for Nuclear Science and Technology, Jeju National University) ;
  • Kang, Kyoung Ah (School of Medicine and Institute for Nuclear Science and Technology, Jeju National University) ;
  • Ryu, Yea Seong (School of Medicine and Institute for Nuclear Science and Technology, Jeju National University) ;
  • Fernando, Pattage Madushan Dilhara Jayatissa (School of Medicine and Institute for Nuclear Science and Technology, Jeju National University) ;
  • Oh, Min Chang (School of Medicine and Institute for Nuclear Science and Technology, Jeju National University) ;
  • Park, Jeong Eon (School of Medicine and Institute for Nuclear Science and Technology, Jeju National University) ;
  • Shilnikova, Kristina (School of Medicine and Institute for Nuclear Science and Technology, Jeju National University) ;
  • Moon, Yu Jin (School of Medicine and Institute for Nuclear Science and Technology, Jeju National University) ;
  • Shin, Dae O (School of Medicine and Institute for Nuclear Science and Technology, Jeju National University) ;
  • Hyun, Jin Won (School of Medicine and Institute for Nuclear Science and Technology, Jeju National University)
  • Received : 2016.05.22
  • Accepted : 2016.08.02
  • Published : 2017.07.01

Abstract

Previously, we demonstrated that galangin (3,5,7-trihydroxyflavone) protects human keratinocytes against ultraviolet B (UVB)-induced oxidative damage. In this study, we investigated the effect of galangin on induction of antioxidant enzymes involved in synthesis of reduced glutathione (GSH), and investigated the associated upstream signaling cascades. By activating nuclear factor-erythroid 2-related factor (Nrf2), galangin treatment significantly increased expression of glutamate-cysteine ligase catalytic subunit (GCLC) and glutathione synthetase (GSS). This activation of Nrf2 depended on extracellular signal-regulated kinases (ERKs) and protein kinase B (AKT) signaling. Inhibition of GSH in galangin-treated cells attenuated the protective effect of galangin against the deleterious effects of UVB. Our results reveal that galangin protects human keratinocytes by activating ERK/AKT-Nrf2, leading to elevated expression of GSH-synthesizing enzymes.

Keywords

References

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