Galangin Activates the ERK/AKT-Driven Nrf2 Signaling Pathway to Increase the Level of Reduced Glutathione in Human Keratinocytes.
10.4062/biomolther.2016.112
- Author:
Susara Ruwan Kumara Madduma HEWAGE
1
;
Mei Jing PIAO
;
Kyoung Ah KANG
;
Yea Seong RYU
;
Pattage Madushan Dilhara Jayatissa FERNANDO
;
Min Chang OH
;
Jeong Eon PARK
;
Kristina SHILNIKOVA
;
Yu Jin MOON
;
Dae O SHIN
;
Jin Won HYUN
Author Information
1. School of Medicine and Institute for Nuclear Science and Technology, Jeju National University, Jeju 63243, Republic of Korea. jinwonh@jejunu.ac.kr
- Publication Type:Original Article
- Keywords:
Galangin;
Reduced glutathione;
Nuclear factor-erythroid 2-related factor;
Glutamate-cysteine ligase catalytic subunit;
Glutathione synthetase
- MeSH:
Catalytic Domain;
Extracellular Signal-Regulated MAP Kinases;
Glutamate-Cysteine Ligase;
Glutathione Synthase;
Glutathione*;
Humans*;
Keratinocytes*;
Proto-Oncogene Proteins c-akt
- From:Biomolecules & Therapeutics
2017;25(4):427-433
- CountryRepublic of Korea
- Language:English
-
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.