Next Article in Journal
Hemi-Synthesis and Anti-Oomycete Activity of Analogues of Isocordoin
Previous Article in Journal
Two New β-Dihydroagarofuran Sesquiterpenes from Celastrus orbiculatus Thunb and Their Anti-Proliferative Activity
Previous Article in Special Issue
Daucosterol Inhibits the Proliferation, Migration, and Invasion of Hepatocellular Carcinoma Cells via Wnt/β-Catenin Signaling
Article Menu
Issue 6 (June) cover image

Export Article

Open AccessArticle
Molecules 2017, 22(6), 969; doi:10.3390/molecules22060969

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

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
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Academic Editor: Diego Muñoz-Torrero
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)
View Full-Text   |   Download PDF [2211 KB, uploaded 10 June 2017]   |  

Abstract

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
Figures

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

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.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]

Molecules EISSN 1420-3049 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top