Effect of 7, 8-dihydroxyflavone on the up-regulation of Nrf2-mediated heme oxygenase-1 expression in hamster lung fibroblasts

• Published in: In vitro cellular & developmental biology. Animal Vol. 50; no. 6; pp. 549 - 554
• Main Authors: Ryu, Min Ju, Kang, Kyoung Ah, Piao, Mei Jing, Kim, Ki Cheon, Zheng, Jian, Yao, Cheng Wen, Cha, Ji Won, Hyun, Chang Lim, Chung, Ha Sook, Park, Jong Cook, Cho, Suk Ju, Hyun, Jin Won
• Format: Journal Article
• Language: English
• Published: Boston Springer-Verlag 01.06.2014; Springer Science + Business Media; Springer US; Society for In Vitro Biology
• Subjects: Active Transport, Cell Nucleus; Animal Genetics and Genomics; Animals; Antibodies; Antioxidants; Biomedical and Life Sciences; Butadienes - pharmacology; Cell Biology; Cell Culture; CELL GROWTH/DIFFERENTIATION/APOPTOSIS; Cell Line; Cell nucleus; Cell Nucleus - metabolism; Cell Survival; cell viability; Cricetinae; Cytoprotection; cytosol; Developmental Biology; Extracellular Signal-Regulated MAP Kinases - antagonists & inhibitors; Extracellular Signal-Regulated MAP Kinases - metabolism; Fibroblasts; Fibroblasts - cytology; Fibroblasts - metabolism; Flavones - pharmacology; hamsters; heme oxygenase (decyclizing); Heme Oxygenase-1 - biosynthesis; Heme Oxygenase-1 - genetics; Heme Oxygenase-1 - metabolism; Hep G2 cells; Life Sciences; Lung - cytology; Lungs; mitogen-activated protein kinase; NF-E2-Related Factor 2 - biosynthesis; NF-E2-Related Factor 2 - genetics; NF-E2-Related Factor 2 - metabolism; Nitriles - pharmacology; Oxidative stress; Oxidative Stress - drug effects; Phosphorylation; protective effect; Protein synthesis; Protein Transport; RNA Interference; RNA, Messenger - biosynthesis; RNA, Small Interfering; Signal Transduction; Stem Cells; transcription factors; Transcriptional regulatory elements; Up-Regulation; Lung fibroblast V79-4 cells; Extracellular signal-regulated kinase; Transcription factor; 7,8-Dihydroxyflavone; Heme oxygenase-1
• ISSN: 1071-2690; 1543-706X
• DOI: 10.1007/s11626-014-9735-4

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.