title: Dieckol enhances the expression of antioxidant and detoxifying enzymes by the activation of Nrf2-MAPK signalling pathway in HepG2 cells.
abstract: Dieckol was previously reported to exhibit antioxidant and anticancer activities in vitro studies. In this study, we characterised the mechanism underlying the dieckol-mediated expression of antioxidant and detoxifying enzymes. Dieckol suppressed the production of intracellular reactive oxygen species in the presence or absence of H2O2 and increased glutathione level in HepG2 cells. Dieckol enhanced the activities of antioxidant enzymes, and the expression of detoxifying enzymes including heme oxygenase-1 (HO-1), NAD(P)H:quinine oxidoreductase 1 (NQO1), and glutathione S-transferase (GST) in HepG2 cells. Enhanced expression of antioxidant and detoxifying enzymes by dieckol was presumed to be the activation of the nuclear factor erythroid-derived 2-like 2 (Nrf2) demonstrated by its nuclear translocation and transcriptional activity via activation of mitogen-activated protein kinases in HepG2 cells. Furthermore, we demonstrated dieckol induced the expression of HO-1 in mouse liver. These results demonstrate that the dieckol-mediated cytoprotection in HepG2 cells is mediated through a ROS-independent up-regulation of antioxidant and detoxifying enzymes via Nrf2 activation as well as its intrinsic antioxidant activity, suggesting that dieckol may be used as a natural cytoprotective agent.
authors.affiliation: Department of Food Science and Nutrition, Pukyong National University, Busan 608-737, South Korea.
authors.forename: Min-Sup
authors.initials: MS
authors.lastname: Lee
authors.affiliation: National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Bonggi
authors.initials: B
authors.lastname: Lee
authors.affiliation: Department of Food Science and Nutrition, Pukyong National University, Busan 608-737, South Korea.
authors.forename: Kyoung-Eun
authors.initials: KE
authors.lastname: Park
authors.affiliation: Department of Pathobiological Science, School of Veterinary Medicine, Louisiana State University, Skip Bertman Drive, Baton Rouge, LA 70803, USA.
authors.forename: Tadanobu
authors.initials: T
authors.lastname: Utsuki
authors.affiliation: Department of Food Science and Nutrition, Chonnam National University, Yeosu 550-749, South Korea.
authors.forename: Taisun
authors.initials: T
authors.lastname: Shin
authors.affiliation: Department of Marine Biology, Pukyong National University, Busan 608-737, South Korea.
authors.forename: Chul Woong
authors.initials: CW
authors.lastname: Oh
authors.affiliation: Department of Food Science and Nutrition, Pukyong National University, Busan 608-737, South Korea. Electronic address: hrkim@pknu.ac.kr.
authors.forename: Hyeung-Rak
authors.initials: HR
authors.lastname: Kim
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001572:Benzofurans / Q000378:metabolism*; D051547:Heme Oxygenase-1 / Q000235:genetics*; D056945:Hep G2 Cells; D006801:Humans; D008297:Male; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics*; D051267:NF-E2-Related Factor 2 / Q000235:genetics*; D017382:Reactive Oxygen Species / Q000378:metabolism; D014162:Transfection
chemical_list: D000975:Antioxidants; D001572:Benzofurans; D051267:NF-E2-Related Factor 2; D017382:Reactive Oxygen Species; C503840:dieckol; D051547:Heme Oxygenase-1; D020928:Mitogen-Activated Protein Kinases
keywords: Dieckol; Glutathione S-transferase; Hemeoxygenase-1; MAPK; NAD(P)H:quinine oxidoreductase 1; Nrf2