The Bacterial Fermentation Product Butyrate Influences Epithelial Signaling via Reactive Oxygen Species-Mediated Changes in Cullin-1 Neddylation
Kumar, A; Wu, H; Collier-Hyams, LS; Kwon, YMan; Hanson, JM; Neish, AS
| HERO ID | 1455989 |
|---|---|
| In Press | No |
| Year | 2009 |
| Title | The Bacterial Fermentation Product Butyrate Influences Epithelial Signaling via Reactive Oxygen Species-Mediated Changes in Cullin-1 Neddylation |
| Authors | Kumar, A; Wu, H; Collier-Hyams, LS; Kwon, YMan; Hanson, JM; Neish, AS |
| Journal | Journal of Immunology |
| Volume | 182 |
| Issue | 1 |
| Page Numbers | 538-546 |
| Abstract | The human enteric flora plays a significant role in intestinal health and disease. Populations of enteric bacteria can inhibit the NF-kappa B pathway by blockade of I kappa B-alpha ubiquitination, a process catalyzed by the E3-SCF(beta-TrCP) ubiquitin ligase. The activity of this ubiquitin ligase is regulated via covalent modification of the Cullin-1 subunit by the ubiquitin-like protein NEDD8. We previously reported that interaction of viable commensal bacteria with mammalian intestinal epithelia] cells resulted in a rapid and reversible generation of reactive oxygen species (ROS) that modulated neddylation of Cullin-1 and resulted in suppressive effects on the NF-kappa B pathway. Herein, we demonstrate that butyrate and other short chain fatty acids supplemented to model human intestinal epithelia in vitro and human tissue ex vivo results in loss of neddylated Cullin-1 and show that physiological concentrations of butyrate modulate the ubiquitination and degradation of a target of the E3-SCF (beta-TrCP) ubiquitin ligase, the NF-kappa B inhibitor I kappa B-alpha. Mechanistically, we show that physiological concentrations of butyrate induces reactive oxygen species that transiently alters the intracellular redox balance and results in inactivation of the NEDD8-conjugating enzyme Ubc12 in a manner similar to effects mediated by viable bacteria. Because the normal flora produces significant amounts of butyrate and other short chain fatty acids, these data provide a functional link between a natural product of the intestinal normal flora and important epithelial inflammatory and proliferative signaling pathways. The Journal of Immunology, 2009, 182: 538- 546. |
| Pmid | 19109186 |
| Wosid | WOS:000262057200063 |
| Is Certified Translation | No |
| Dupe Override | No |
| Comments | Source: Web of Science WOS:000262057200063 |
| Is Public | Yes |