Sodium 4-phenylbutyrate upregulates ENaC and sodium absorption in T84 cells.
Butyrate and other short-chain fatty acids (SCFA), produced by colonic bacterial flora, affect numerous epithelial cell functions. To better understand how SCFA regulate ion transport, we investigated the effects of 4-phenylbutyrate (4-PBA) on Na(+) absorption in T84 cells. Under standard cell culture conditions, the short circuit current did not display any amiloride-sensitive Na(+) absorption and was wholly representative of Cl(-) secretion. However, when T84 cells were grown in the presence of 5 mM 4-PBA, a gradual appearance of amiloride-sensitive Na(+) channel (ENaC) activity was observed that reached a plateau after 24 h. Quantitative RT-PCR and Western blot studies of ENaC subunit expression indicated that 4-PBA stimulated alpha and gamma subunits. Trichostatin A, an inhibitor of histone deacetylase, mimicked the effects of 4-PBA, suggesting that 4-PBA affects ENaC expression by inhibiting deacetylases. 4-PBA had no effect on ENaC expression in airway epithelial cells indicating tissue-specific effect. We conclude that butyrate plays an important role in regulating colonic Na(+) absorption by increasing ENaC transcription and activity.
Iordache
Claudiu
C
Department of Physiology, University of Alberta, 7-46 Med Sci Bldg., Edmonton, Alberta, Canada.
Duszyk
Marek
M
D002087:Butyrates / Q000494:pharmacology; D002478:Cells, Cultured; D053503:Epithelial Sodium Channels / Q000378:metabolism*; D006801:Humans; D007408:Intestinal Absorption / Q000187:drug effects*; D010654:Phenylbutyrates / Q000494:pharmacology*; D012964:Sodium / Q000378:metabolism*; D015854:Up-Regulation
D002087:Butyrates; D053503:Epithelial Sodium Channels; D010654:Phenylbutyrates; C075773:4-phenylbutyric acid; D012964:Sodium