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    Please use this identifier to cite or link to this item: http://asiair.asia.edu.tw/ir/handle/310904400/25281


    Title: Docosahexaenoic acid inhibition of inflammation is partially via cross-talk betweenNrf2/heme oxygenase 1 and IKK/NF-κB pathways
    Authors: 楊雅甄;Yang, Ya-Chen
    Contributors: 保健營養生技學系
    Keywords: Docosahexaenoic acid (DHA);Heme oxygenase 1 (HO-1);Intercellular adhesion molecule 1 (ICAM-1);Nuclear factor erythroid 2-related factor 2 (Nrf2);Tumor necrosis factor-alpha (TNF-α)
    Date: 2013-01
    Issue Date: 2013-07-11 14:02:17 (UTC+8)
    Abstract: We examined the underlying mechanisms involved in n-3 docosahexaenoic acid (DHA) inhibition of inflammation in EA.hy926 cells. The present results demonstrated that pretreatment with DHA (50 and 100 μM) inhibited tumor necrosis factor-alpha (TNF-α)-induced intercellular adhesion molecule 1 (ICAM-1) protein, mRNA expression and promoter activity. In addition, TNF-α-stimulated inhibitory kappa B (IκB) kinase (IKK) phosphorylation, IκB phosphorylation and degradation, p65 nuclear translocation, and nuclear factor-κB (NF-κB) and DNA binding activity were attenuated by pretreatment with DHA. DHA triggered early-stage and transient reactive oxygen species (ROS) generation and significantly increased the protein expression of heme oxygenase 1 (HO-1), induced nuclear factor erythroid 2-related factor 2 (Nrf2) translocation to the nucleus and up-regulated antioxidant response element (ARE)-luciferase reporter activity. Moreover, DHA inhibited Nrf2 ubiquitination and proteasome activity. DHA activated Akt, p38 and ERK1/2 phosphorylation, and specific inhibitors of respective pathways attenuated DHA-induced Nrf2 nuclear translocation and HO-1 expression. Transfection with HO-1 siRNA knocked down HO-1 expression and partially reversed the DHA-mediated inhibition of TNF-α-induced p65 nuclear translocation and ICAM-1 expression. Importantly, we show for the first time that HO-1 plays a down-regulatory role in NF-κB nuclear translocation, and inhibition of Nrf2 ubiquitination and proteasome activity are involved in increased cellular Nrf2 level by DHA. In this study, we show that HO-1 plays a down-regulatory role in NF-κB nuclear translocation and that the protective effect of DHA against inflammation is partially via up-regulation of Nrf2-mediated HO-1 expression and inhibition of IKK/NF-κB signaling pathway.
    Copyright © 2013 Elsevier Inc. All rights reserved.
    Relation: JOURNAL OF NUTRITIONAL BIOCHEMISTRY, 24:204-212
    Appears in Collections:[食品營養與保健生技學系] 期刊論文

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