Effects of Eicosapentaenoic Acid on the Cytoprotection Through Nrf2-Mediated Heme Oxygenase-1 in Human Endothelial Cells

Seung Eun Lee, Gun Dong Kim, Hana Yang, Gun Woo Son, Hye Rim Park, Jeong Je Cho, Hyun Jong Ahn, Cheung Seog Park, Yong Seek Park

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

Consumption of omega-3 polyunsaturated fatty acid, particularly eicosapentaenoic acid (EPA), is associated with a significant reduction in the risk of developing cardiovascular disease. The aim of this study was to investigate whether heme oxygenase-1 (HO-1) induction contributes to the cytoprotective effects of EPA in endothelial cells threatened with oxidative damage. In this study, we investigated the effect of EPA on the induction of HO-1 by NF-E2-related factor 2 (Nrf2) in human umbilical vein endothelial cells. In cells treated with low concentrations of EPA (10-25 μM), HO-1 expression increased in a time- and concentration-dependent manner. Additionally, EPA treatment increased Nrf2 nuclear translocation and antioxidant response element activity, leading to the upregulation of HO-1 expression. Furthermore, treatment with EPA reduced hydrogen peroxide (H2O2)-induced cell death. The reduction in cell death was reversed by treatment with zinc protoporphyrin, an inhibitor of HO-1, indicating that HO-1 contributed to the protective effect of EPA. These data suggest that EPA protects against H2O2-induced oxidative stress in endothelial cells by activating Nrf2 and inducting HO-1 expression.

Original languageEnglish (US)
Pages (from-to)108-117
Number of pages10
JournalJournal of Cardiovascular Pharmacology
Volume66
Issue number1
DOIs
StatePublished - Jul 23 2015

Keywords

  • EPA
  • HO-1
  • Nrf2
  • endothelial cells
  • oxidative stress

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