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The enhancement of phase 2 enzyme activities by sodium butyrate in normal intestinal epithelial cells is associated with Nrf2 and p53

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Abstract

Dietary fiber fermentation by the colonic bacterial flora produces short-chain fatty acids, acetate, propionate and butyrate. Among them, butyrate is considered to be the major energy substrate for colonocytes and, at least in rats, seems to protect against colonic carcinogenesis. In this study, we examined the effect and the mechanisms of short-chain fatty acids on the activity of phase 2 enzymes. Sodium butyrate increased phase 2 enzyme activities in normal rat small intestine epithelial cells, Glutathione S-transferase and NAD(P)H:quinone oxidoreductase (NQO) in a dose-dependent manner; however, other short-chain fatty acids did not increase them. The mechanism of the induction of phase 2 enzymes with sodium butyrate sodium butyrate, but not other short-chain fatty acids was related to the increase of NF-E2-related factor 2 (Nrf2) nuclear translocation and the decrease in the levels of nuclear fraction p53. Sodium butyrate also caused enhancement of Nrf2 mRNA levels and suppression of p53 mRNA levels. Sodium butyrate enhances the activities of phase 2 enzymes via an increase in the Nrf2 protein levels in the nucleus and a decrease in the mRNA and protein levels of p53.

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Acknowledgments

This study was partially supported by a Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of the Science (21500783).

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Authors and Affiliations

  1. Department of Food and Human Health Sciences, Graduate School of Human Life Science, Osaka City University, 3-3-138 Sugimoto, Sumiyoshi-ku, Osaka, 558-8585, Japan

    Keisuke Yaku, Yuka Enami, Chika Kurajyo, Isao Matsui-Yuasa, Yotaro Konishi & Akiko Kojima-Yuasa

  2. Faculty of Education, Wakayama University, Wakayama, Japan

    Isao Matsui-Yuasa

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  1. Keisuke Yaku
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  2. Yuka Enami
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  3. Chika Kurajyo
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Correspondence to Akiko Kojima-Yuasa.

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Yaku, K., Enami, Y., Kurajyo, C. et al. The enhancement of phase 2 enzyme activities by sodium butyrate in normal intestinal epithelial cells is associated with Nrf2 and p53. Mol Cell Biochem 370, 7–14 (2012). https://doi.org/10.1007/s11010-012-1392-x

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  • DOI: https://doi.org/10.1007/s11010-012-1392-x

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