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Oat avenanthramides induce heme oxygenase‐1 expression via Nrf2‐mediated signaling in HK‐2 cells
Author(s) -
Fu Junsheng,
Zhu Yingdong,
Yerke Aaron,
Wise Mitchell L.,
Johnson Jodee,
Chu YiFang,
Sang Shengmin
Publication year - 2015
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.201500250
Subject(s) - heme oxygenase , chemistry , heme , reactive oxygen species , ly294002 , antioxidant , p38 mitogen activated protein kinases , pi3k/akt/mtor pathway , keap1 , mapk/erk pathway , microbiology and biotechnology , chromosomal translocation , signal transduction , protein kinase b , oxidative stress , biochemistry , transcription factor , biology , enzyme , gene
Scope Numerous studies have shown that avenanthramides (AVAs), unique compounds found in oats, are strong antioxidants, though the mechanism of action remains unclear. Here, we investigated whether AVAs affect heme oxygenase‐1 (HO‐1) expression through the activation of Nrf2 translocation. Methods and results We investigated the effects AVA 2c, 2f, and 2p on HK‐2 cells, and found that AVAs could significantly increase HO‐1 expression in both a dose‐ and time‐dependent manner. Furthermore, we found that AVA‐induced HO‐1 expression is mediated by Nrf2 translocation. The addition of N‐acetylcysteine (NAC), but not specific inhibitors of p38 (SB202190), PI3K (LY294002), and MEK1 (PD098059) attenuated AVA‐induced HO‐1 expression, demonstrating an important role for reactive oxygen species, but not PI3K or MAPK activation, in activating the HO‐1 pathway. Moreover, hydrogenation of the double bond of the functional α,β ‐unsaturated carbonyl group of AVAs eliminated their effects on HO‐1 expression, suggesting that this group is crucial for the antioxidant activity of AVAs. Conclusion Our results suggest a novel mechanism whereby AVAs exert an antioxidant function on human health. Further investigation of these markers in human is warranted to explore the beneficial health effects of whole grain oat intake.