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Oat Avenanthramides Induce Heme Oxygengase‐1 Expression via Nrf2‐mediated Signaling in HK‐2 Cells
Author(s) -
Sang Shengmin,
Fu Junsheng,
Zhu Yingdong,
Yerke Aaron,
Wise Mitchell,
Johnson Jodee,
Chu YiFang
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.390.1
Subject(s) - heme oxygenase , chemistry , heme , chromosomal translocation , p38 mitogen activated protein kinases , mapk/erk pathway , pi3k/akt/mtor pathway , microbiology and biotechnology , mechanism of action , signal transduction , in vitro , biochemistry , pharmacology , biology , enzyme , gene
Laboratory and human studies have shown that avenanthramides (AVAs), unique compounds found in oats, are strong antioxidants. However, their specific mechanism of action remains unclear. The objective was to investigate the abilities of the three major AVAs in oats (2c, 2p, 2f) to activate Nrf2 nuclear translocation leading to the activation of phase II detoxification genes in vitro . The three AVAs significantly increased heme oxygenase‐1 (HO‐1) expression in HK‐2 cells in both a dose‐ and time‐dependent manner. Mechanistic studies show that HO‐1 expression induced by AVAs is mediated via Nrf2 translocation. All three AVAs stimulated Nrf2 nuclear translocation in both a dose‐ and time‐dependent manner. The addition of N‐acetylcysteine (NAC) suppressed the HO‐1 expression induced by 2c, 2f, and 2p, establishing that ROS plays a role on the up‐regulation of HO‐1 by AVAs. Pretreatment of cells with inhibitors of p38, PI3K, and MEK1 did not attenuate AVA‐induced HO‐1 expression, suggesting that HO‐1 expression is not associated with PI3K or MAPK activation. Hydrogenation of the double bond of the functional α,β ‐unsaturated carbonyl group of AVAs eliminated their effects on HO‐1 expression, suggesting a role for the functional α,β ‐unsaturated carbonyl group in the mechanism of action of AVAs. These results show the ability of AVAs to induce HO‐1 expression in HK‐2 cells. This action appears to be mediated by Nrf2 activation and is not associated with PI3K or MAPK activation.