Dieckol enhances the expression of antioxidant and detoxifying enzymes by the activation of Nrf2–MAPK signalling pathway in HepG2 cells. (1st May 2015)

• Record Type: Journal Article
• Authors: Lee, Min-Sup; Lee, Bonggi; Park, Kyoung-Eun; Utsuki, Tadanobu; Shin, Taisun; Oh, Chul Woong; Kim, Hyeung-Rak
• Is Part Of: Food chemistry. Volume 174(2015)
• Page Start: 538
• Page End: 546
• Publication Date: 2015-05-01
• Subjects: ALT alanine aminotransferase -- ARE antioxidant response element -- AST aspartate aminotransferase -- BSA bovine serum albumin -- DAPI 4′, 6-diamidino-2-phenylindole -- DCF-DA 2′, 7′-dichlorofluorescein diacetate -- DMSO dimethyl sulfoxide -- DPPH 2, 2-diphenyl-1-picrylhydrazyl -- ECL enhanced chemiluminescence -- FBS fetal bovine serum -- GSH glutathione -- GST glutathione S-transferase -- HO heme oxygenase -- Keap1 Kelch-like ECH-associated protein 1 -- MAPKs mitogen-activated protein kinases -- MEM minimum essential medium -- MTS 3-(4, 5-dimethyl-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium -- NAC N-acetylcysteine -- NF-κB nuclear factor-kappaB -- NQO1 NAD(P)H:quinine oxidoreductase 1 -- NF-E2 nuclear factor erythroid 2 -- Nrf2 nuclear factor erythroid-derived 2-like 2 -- PARP poly(ADP-ribose)polymerase -- PBS phosphate-buffered saline -- PMSF phenylmethylsulfonyl fluoride -- ROS reactive oxygen species -- SOD superoxide dismutase -- TBS Tris-buffered saline; Dieckol -- Hemeoxygenase-1 -- NAD(P)H:quinine oxidoreductase 1 -- Glutathione S-transferase -- Nrf2 -- MAPK; Food -- Analysis -- Periodicals; Food -- Composition -- Periodicals; 664
• DOI: 10.1016/j.foodchem.2014.11.090
• Languages: English
• ISSNs: 0308-8146

Abstract

Highlights: Dieckol reduced oxidative stress and induced GSH level in HepG2 cells. Dieckol increased SOD, catalase, and GST enzyme activity. Dieckol enhanced HO-1, NQO-1, and GST expression in vitro, and HO-1 in vivo . Antioxidative enzyme expression was upregulated by activation of Nrf2 and MAPKs. 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 H2 O2 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.