Journal Articles

Oat Avenanthramides Induce Heme Oxygengase-1 Expression via Nrf2-mediated Signaling in HK-2 Cells

April 07, 2015

Oat Avenanthramides Induce Heme Oxygengase-1 Expression via Nrf2-mediated Signaling in HK-2 Cells, Apr 2015, The FASEB Journal, Shengmin Sang1, Junsheng Fu1, Yingdong Zhu1, Aaron Yerke1, Mitchell Wise2, Jodee Johnson3 and YiFang Chu3

  1. 1Center for Excellence in Post-Harvest Technologies North Carolina Agricultural and Technical State University Kannapolis NC United States
  2. 2Cereal Crops Research Unit USDA Madison WI United States
  3. 3Quaker Oats Center of Excellence PepsiCo R&D Nutrition Barrington IL United States

Oat Avenanthramides Induce Heme Oxygengase-1 Expression via Nrf2-mediated Signaling in HK-2 Cells

Abstract

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.

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