Oat avenanthramides induce heme oxygenase-1 expression via Nrf2-mediated signaling in HK-2 cells.
METHODS
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.


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.


CONCLUSIONS
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.
College of Life Sciences, Fujian Agriculture and Forestry University, Fuzhou City, P. R. China.|Center for Excellence in Post-Harvest Technologies, North Carolina Agricultural and Technical State University, North Carolina Research Campus, Kannapolis, NC, USA.
Junsheng
J
Fu
Center for Excellence in Post-Harvest Technologies, North Carolina Agricultural and Technical State University, North Carolina Research Campus, Kannapolis, NC, USA.
Yingdong
Y
Zhu
Center for Excellence in Post-Harvest Technologies, North Carolina Agricultural and Technical State University, North Carolina Research Campus, Kannapolis, NC, USA.
Aaron
A
Yerke
USDA, Cereal Crops Research Unit, Madison, WI, USA.
Mitchell L
ML
Wise
Quaker Oats Center of Excellence, PepsiCo R&D Nutrition, Barrington, IL, USA.
Jodee
J
Johnson
Quaker Oats Center of Excellence, PepsiCo R&D Nutrition, Barrington, IL, USA.
YiFang
Y
Chu
Center for Excellence in Post-Harvest Technologies, North Carolina Agricultural and Technical State University, North Carolina Research Campus, Kannapolis, NC, USA.|Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Shengmin
S
Sang
D000975:Antioxidants / Q000494:pharmacology; D018554:Avena / Q000737:chemistry*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D006801:Humans; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D021381:Protein Transport / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D062367:ortho-Aminobenzoates / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D000975:Antioxidants; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D047428:Protein Kinase Inhibitors; D017382:Reactive Oxygen Species; D062367:ortho-Aminobenzoates; C514463:avenanthramide-2C; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1; D048051:p38 Mitogen-Activated Protein Kinases
Antioxidant; Avenanthramides; HO-1; Nrf2; Oats