title: Effect of 7, 8-dihydroxyflavone on the up-regulation of Nrf2-mediated heme oxygenase-1 expression in hamster lung fibroblasts.
abstract: The cytoprotective mechanism of 7, 8-dihydroxyflavone (DHF) against oxidative stress-induced cell damage with respect to its stimulatory effect on the expression of heme oxygenase-1 (HO-1), a potent antioxidant enzyme, was investigated in the present study. Up-regulation of HO-1 expression by DHF was both dose and time dependent in lung fibroblast V79-4 cells. DHF also increased the protein expression level of the transcription factor nuclear factor erythroid-2-related factor 2 (Nrf2), and induced the translocation of Nrf2 from the cytosol into the nucleus, leading to elevated HO-1 expression. The siNrf2 RNA-transfection attenuated HO-1 expression induced by DHF treatment. In addition, DHF induced the activation of extracellular signal-regulated kinase (ERK), while U0126 (a specific pharmacological inhibitor of ERK kinase) abrogated DHF-activated Nrf2 and HO-1 expression. This suggests that DHF increased the levels of Nrf2 and HO-1 via ERK-dependent pathways. Furthermore, DHF significantly prevented the reduction of cell viability in response to oxidative stress; however, U0126 attenuated the protective effect of DHF. Taken together, these results demonstrate that DHF protected cells from oxidative stress via the activation of an ERK/Nrf2/HO-1 signaling pathway.
authors.affiliation: Food and Nutrition, Duksung Women's University, Seoul, 132-714, Republic of Korea.
authors.forename: Min Ju
authors.initials: MJ
authors.lastname: Ryu
authors.forename: Kyoung Ah
authors.initials: KA
authors.lastname: Kang
authors.forename: Mei Jing
authors.initials: MJ
authors.lastname: Piao
authors.forename: Ki Cheon
authors.initials: KC
authors.lastname: Kim
authors.forename: Jian
authors.initials: J
authors.lastname: Zheng
authors.forename: Cheng Wen
authors.initials: CW
authors.lastname: Yao
authors.forename: Ji Won
authors.initials: JW
authors.lastname: Cha
authors.forename: Chang Lim
authors.initials: CL
authors.lastname: Hyun
authors.forename: Ha Sook
authors.initials: HS
authors.lastname: Chung
authors.forename: Jong Cook
authors.initials: JC
authors.lastname: Park
authors.forename: Suk Ju
authors.initials: SJ
authors.lastname: Cho
authors.forename: Jin Won
authors.initials: JW
authors.lastname: Hyun
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D002070:Butadienes / Q000494:pharmacology; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D002470:Cell Survival; D006224:Cricetinae; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D047309:Flavones / Q000494:pharmacology*; D051547:Heme Oxygenase-1 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D008168:Lung / Q000166:cytology; D051267:NF-E2-Related Factor 2 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D009570:Nitriles / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects*; D010766:Phosphorylation; D021381:Protein Transport; D034622:RNA Interference; D012333:RNA, Messenger / Q000096:biosynthesis; D034741:RNA, Small Interfering; D015398:Signal Transduction; D015854:Up-Regulation
chemical_list: C485383:6,7-dihydroxyflavone; D002070:Butadienes; D047309:Flavones; D051267:NF-E2-Related Factor 2; D009570:Nitriles; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C113580:U 0126; D051547:Heme Oxygenase-1; D048049:Extracellular Signal-Regulated MAP Kinases