Regulation of the rat NHE3 gene promoter by sodium butyrate

Pawel R Kiela, E. R. Hines, J. F. Collins, Fayez K Ghishan

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

Short-chain fatty acids, and especially butyrate (NaB), stimulate sodium and water absorption by inducing colonic Na+/H+ exchange (NHE). NaB induces NHE3 activity and protein and mRNA expression both in vivo and in vitro. NaB, as a histone deacetylase (HDAC) inhibitor, regulates gene transcription. We therefore studied whether NaB regulates transcription of the rat NHE3 promoter in transiently transfected Caco-2 cells. NaB (5 mM) strongly stimulated reporter gene activity, and this stimulation was prevented with actinomycin D, indicating transcriptional activation. NaB effects on the NHE3 promoter depended on the activity of Ser/Thr kinases, in particular, protein kinase A (PKA). However, PKA stimulation alone did not have an effect on promoter activity, and it did not act synergistically with NaB. Another HDAC inhibitor, Trichostatin A (TSA), stimulated NHE3 promoter in a Ser/Thr kinase-independent fashion. The putative NaB-responsive elements were localized within -320/-34 bp of the NHE3 promoter. These findings suggest that PKA mediates NaB effects on NHE3 gene transcription and that the mechanism of NaB action is different from that of TSA.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume281
Issue number4 44-4
StatePublished - 2001

Fingerprint

Butyric Acid
trichostatin A
Cyclic AMP-Dependent Protein Kinases
Histone Deacetylase Inhibitors
Phosphotransferases
Genes
Caco-2 Cells
Volatile Fatty Acids
Butyrates
Dactinomycin
Reporter Genes
Transcriptional Activation
Sodium
Messenger RNA
Water
Proteins

Keywords

  • Protein kinase A
  • Serine/threonine kinases
  • Short-chain fatty acids
  • Signal transduction
  • Sodium-hydrogen exchanger

ASJC Scopus subject areas

  • Gastroenterology
  • Physiology
  • Physiology (medical)

Cite this

Regulation of the rat NHE3 gene promoter by sodium butyrate. / Kiela, Pawel R; Hines, E. R.; Collins, J. F.; Ghishan, Fayez K.

In: American Journal of Physiology - Gastrointestinal and Liver Physiology, Vol. 281, No. 4 44-4, 2001.

Research output: Contribution to journalArticle

@article{1ee9b82a1ca2447ea446a232a7a919bf,
title = "Regulation of the rat NHE3 gene promoter by sodium butyrate",
abstract = "Short-chain fatty acids, and especially butyrate (NaB), stimulate sodium and water absorption by inducing colonic Na+/H+ exchange (NHE). NaB induces NHE3 activity and protein and mRNA expression both in vivo and in vitro. NaB, as a histone deacetylase (HDAC) inhibitor, regulates gene transcription. We therefore studied whether NaB regulates transcription of the rat NHE3 promoter in transiently transfected Caco-2 cells. NaB (5 mM) strongly stimulated reporter gene activity, and this stimulation was prevented with actinomycin D, indicating transcriptional activation. NaB effects on the NHE3 promoter depended on the activity of Ser/Thr kinases, in particular, protein kinase A (PKA). However, PKA stimulation alone did not have an effect on promoter activity, and it did not act synergistically with NaB. Another HDAC inhibitor, Trichostatin A (TSA), stimulated NHE3 promoter in a Ser/Thr kinase-independent fashion. The putative NaB-responsive elements were localized within -320/-34 bp of the NHE3 promoter. These findings suggest that PKA mediates NaB effects on NHE3 gene transcription and that the mechanism of NaB action is different from that of TSA.",
keywords = "Protein kinase A, Serine/threonine kinases, Short-chain fatty acids, Signal transduction, Sodium-hydrogen exchanger",
author = "Kiela, {Pawel R} and Hines, {E. R.} and Collins, {J. F.} and Ghishan, {Fayez K}",
year = "2001",
language = "English (US)",
volume = "281",
journal = "American Journal of Physiology",
issn = "0363-6143",
publisher = "American Physiological Society",
number = "4 44-4",

}

TY - JOUR

T1 - Regulation of the rat NHE3 gene promoter by sodium butyrate

AU - Kiela, Pawel R

AU - Hines, E. R.

AU - Collins, J. F.

AU - Ghishan, Fayez K

PY - 2001

Y1 - 2001

N2 - Short-chain fatty acids, and especially butyrate (NaB), stimulate sodium and water absorption by inducing colonic Na+/H+ exchange (NHE). NaB induces NHE3 activity and protein and mRNA expression both in vivo and in vitro. NaB, as a histone deacetylase (HDAC) inhibitor, regulates gene transcription. We therefore studied whether NaB regulates transcription of the rat NHE3 promoter in transiently transfected Caco-2 cells. NaB (5 mM) strongly stimulated reporter gene activity, and this stimulation was prevented with actinomycin D, indicating transcriptional activation. NaB effects on the NHE3 promoter depended on the activity of Ser/Thr kinases, in particular, protein kinase A (PKA). However, PKA stimulation alone did not have an effect on promoter activity, and it did not act synergistically with NaB. Another HDAC inhibitor, Trichostatin A (TSA), stimulated NHE3 promoter in a Ser/Thr kinase-independent fashion. The putative NaB-responsive elements were localized within -320/-34 bp of the NHE3 promoter. These findings suggest that PKA mediates NaB effects on NHE3 gene transcription and that the mechanism of NaB action is different from that of TSA.

AB - Short-chain fatty acids, and especially butyrate (NaB), stimulate sodium and water absorption by inducing colonic Na+/H+ exchange (NHE). NaB induces NHE3 activity and protein and mRNA expression both in vivo and in vitro. NaB, as a histone deacetylase (HDAC) inhibitor, regulates gene transcription. We therefore studied whether NaB regulates transcription of the rat NHE3 promoter in transiently transfected Caco-2 cells. NaB (5 mM) strongly stimulated reporter gene activity, and this stimulation was prevented with actinomycin D, indicating transcriptional activation. NaB effects on the NHE3 promoter depended on the activity of Ser/Thr kinases, in particular, protein kinase A (PKA). However, PKA stimulation alone did not have an effect on promoter activity, and it did not act synergistically with NaB. Another HDAC inhibitor, Trichostatin A (TSA), stimulated NHE3 promoter in a Ser/Thr kinase-independent fashion. The putative NaB-responsive elements were localized within -320/-34 bp of the NHE3 promoter. These findings suggest that PKA mediates NaB effects on NHE3 gene transcription and that the mechanism of NaB action is different from that of TSA.

KW - Protein kinase A

KW - Serine/threonine kinases

KW - Short-chain fatty acids

KW - Signal transduction

KW - Sodium-hydrogen exchanger

UR - http://www.scopus.com/inward/record.url?scp=0034786320&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034786320&partnerID=8YFLogxK

M3 - Article

VL - 281

JO - American Journal of Physiology

JF - American Journal of Physiology

SN - 0363-6143

IS - 4 44-4

ER -