Enhancement of phase 2 enzyme activities with sodium butyrate is associated with the nuclear translocation of Nrf2 and p53

Abstract

IntroductionDietary 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.ResultsSodium butyrate increased phase 2 enzymes, GST and NQO in a dose‐dependent manner, however, other short chain fatty acids did not increase these activities. The mechanism of the induction of phase 2 enzymes with sodium butyrate was related to the increase in the Nrf2 and Nrf2/c‐jun complex protein levels in the nucleus. These results suggested that the Nrf2/c‐jun nuclear translocation levels were more important to the induction of phase 2 enzymes than the Nrf2 levels themselves. Furthermore, sodium butyrate, but not other short chain fatty acids, caused the decrease in the levels of nuclear fraction p53 in a dose‐dependent manner.ConclusionThese results suggested that sodium butyrate brings about the increase in the activities of phase 2 enzymes via an increase in the Nrf2 and Nrf2/c‐jun complex protein levels in the nucleus and a decrease in the levels of nuclear fraction p53.