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Open AccessArticle

Docosahexaenoic Acid Induces Expression of Heme Oxygenase-1 and NAD(P)H:quinone Oxidoreductase through Activation of Nrf2 in Human Mammary Epithelial Cells

by 1,2,†, 1,†, 1,3, 4 and 1,2,3,*
1
Tumor Microenvironment Global Core Research Center and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 08826 Korea
2
Cancer Research Institute, Seoul National University, Seoul 03080, Korea
3
Department of Molecular Medicine and Biopharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 08826, Korea
4
Department of Food and Nutrition, College of Human Ecology, Sungshin Women’s University, Seoul 01133, Korea
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: Diego Muñoz-Torrero
Molecules 2017, 22(6), 969; https://doi.org/10.3390/molecules22060969
Received: 6 March 2017 / Revised: 4 June 2017 / Accepted: 5 June 2017 / Published: 10 June 2017
(This article belongs to the Special Issue Cancer Chemoprevention)
Docosahexaenoic acid (DHA), an ω-3 fatty acid abundant in fish oils, has diverse health beneficial effects, such as anti-oxidative, anti-inflammatory, neuroprotective, and chemopreventive activities. In this study, we found that DHA induced expression of two representative antioxidant/cytoprotective enzymes, heme oxygenase-1 (HO-1) and NAD(P)H:quinone oxidoreductase (NQO1), in human mammary epithealial (MCF-10A) cells. DHA-induced upregulation of these enzymes was accompanied by enhanced translocation of the redox-sensitive transcription factor Nrf2 into the nucleus and its binding to antioxidant response element. Nrf2 gene silencing by siRNA abolished the DHA-induced expression of HO-1 and NQO1 proteins. When MCF-10A cells were transfected with mutant constructs in which the cysteine 151 or 288 residue of Keap1 was replaced by serine, DHA-induced expression of HO-1 and NQO1 was markedly reduced. Moreover, DHA activated protein kinase C (PKC)δ and induced Nrf2 phosphorylation. DHA-induced phosphorylation of Nrf2 was abrogated by the pharmacological PKCδ inhibitor rottlerin or siRNA knockdown of its gene expression. The antioxidants N-acetyl-l-cysteine and Trolox attenuated DHA-induced activation of PKCδ, phosphorylation of Nrf2, and and its target protein expression. In conclusion, DHA activates Nrf2, possibly through modification of critical Keap1 cysteine 288 residue and PKCδ-mediated phosphorylation of Nrf2, leading to upregulation of HO-1 and NQO1 expression. View Full-Text
Keywords: docosahexaenoic acid; ω-3 polyunsaturated fatty acids; heme oxygenase-1; NAD(P)H:quinone oxidoreductase; nrf2 docosahexaenoic acid; ω-3 polyunsaturated fatty acids; heme oxygenase-1; NAD(P)H:quinone oxidoreductase; nrf2
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MDPI and ACS Style

Bang, H.-Y.; Park, S.-A.; Saeidi, S.; Na, H.-K.; Surh, Y.-J. Docosahexaenoic Acid Induces Expression of Heme Oxygenase-1 and NAD(P)H:quinone Oxidoreductase through Activation of Nrf2 in Human Mammary Epithelial Cells. Molecules 2017, 22, 969.

AMA Style

Bang H-Y, Park S-A, Saeidi S, Na H-K, Surh Y-J. Docosahexaenoic Acid Induces Expression of Heme Oxygenase-1 and NAD(P)H:quinone Oxidoreductase through Activation of Nrf2 in Human Mammary Epithelial Cells. Molecules. 2017; 22(6):969.

Chicago/Turabian Style

Bang, Hye-Yoon; Park, Sin-Aye; Saeidi, Soma; Na, Hye-Kyung; Surh, Young-Joon. 2017. "Docosahexaenoic Acid Induces Expression of Heme Oxygenase-1 and NAD(P)H:quinone Oxidoreductase through Activation of Nrf2 in Human Mammary Epithelial Cells" Molecules 22, no. 6: 969.

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