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Title: Transcriptional regulation of the human Na{sup +}/H{sup +} exchanger NHE3 by serotonin in intestinal epithelial cells

Abstract

Serotonin (5-HT) decreases NHE2 and NHE3 activities under acute conditions in human intestinal epithelial cells. Here, we have investigated the effects of 5-HT on expression of the human NHE3 gene and the mechanisms underlying its transcriptional regulation in differentiated C2BBe1 cells. Treatment of the human intestinal epithelial cell line, C2BBe1, with 5-HT (20 {mu}M) resulted in a significant decrease in NHE3 mRNA and protein expression. In transient transfection studies, 5-HT repressed the NHE3 promoter activity by {approx}55%. The repression of the NHE3 promoter activity in response to 5-HT was accompanied by reduced DNA-binding activity of transcription factors Sp1 and Sp3 to the NHE3 promoter without alteration in their nuclear levels. Pharmacological inhibitors of protein kinase C reversed the inhibitory effect of 5-HT on the promoter activity. Our data indicate that 5-HT suppresses the transcriptional activity of the NHE3 promoter and this effect may be mediated by PKC{alpha} and modulation of DNA-binding affinities of Sp1 and Sp3.

Authors:
; ; ;  [1]; ;  [1];  [1]
  1. Section of Digestive Diseases and Nutrition, Department of Medicine, University of Illinois at Chicago, 840 S. Wood Street, Chicago, IL 60612 (United States)
Publication Date:
OSTI Identifier:
22199683
Resource Type:
Journal Article
Journal Name:
Biochemical and Biophysical Research Communications
Additional Journal Information:
Journal Volume: 382; Journal Issue: 3; Other Information: Copyright (c) 2009 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0006-291X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; AFFINITY; DNA; GENE REGULATION; GENES; MESSENGER-RNA; PROMOTERS; SEROTONIN; SODIUM IONS; TRANSCRIPTION FACTORS

Citation Formats

Amin, Md Ruhul, Ghannad, Leda, Othman, Ahmad, Gill, Ravinder K., Dudeja, Pradeep K., Ramaswamy, Krishnamurthy, Jesse Brown VAMC, Chicago, IL 60612, and Malakooti, Jaleh. Transcriptional regulation of the human Na{sup +}/H{sup +} exchanger NHE3 by serotonin in intestinal epithelial cells. United States: N. p., 2009. Web. doi:10.1016/J.BBRC.2009.03.087.
Amin, Md Ruhul, Ghannad, Leda, Othman, Ahmad, Gill, Ravinder K., Dudeja, Pradeep K., Ramaswamy, Krishnamurthy, Jesse Brown VAMC, Chicago, IL 60612, & Malakooti, Jaleh. Transcriptional regulation of the human Na{sup +}/H{sup +} exchanger NHE3 by serotonin in intestinal epithelial cells. United States. https://doi.org/10.1016/J.BBRC.2009.03.087
Amin, Md Ruhul, Ghannad, Leda, Othman, Ahmad, Gill, Ravinder K., Dudeja, Pradeep K., Ramaswamy, Krishnamurthy, Jesse Brown VAMC, Chicago, IL 60612, and Malakooti, Jaleh. 2009. "Transcriptional regulation of the human Na{sup +}/H{sup +} exchanger NHE3 by serotonin in intestinal epithelial cells". United States. https://doi.org/10.1016/J.BBRC.2009.03.087.
@article{osti_22199683,
title = {Transcriptional regulation of the human Na{sup +}/H{sup +} exchanger NHE3 by serotonin in intestinal epithelial cells},
author = {Amin, Md Ruhul and Ghannad, Leda and Othman, Ahmad and Gill, Ravinder K. and Dudeja, Pradeep K. and Ramaswamy, Krishnamurthy and Jesse Brown VAMC, Chicago, IL 60612 and Malakooti, Jaleh},
abstractNote = {Serotonin (5-HT) decreases NHE2 and NHE3 activities under acute conditions in human intestinal epithelial cells. Here, we have investigated the effects of 5-HT on expression of the human NHE3 gene and the mechanisms underlying its transcriptional regulation in differentiated C2BBe1 cells. Treatment of the human intestinal epithelial cell line, C2BBe1, with 5-HT (20 {mu}M) resulted in a significant decrease in NHE3 mRNA and protein expression. In transient transfection studies, 5-HT repressed the NHE3 promoter activity by {approx}55%. The repression of the NHE3 promoter activity in response to 5-HT was accompanied by reduced DNA-binding activity of transcription factors Sp1 and Sp3 to the NHE3 promoter without alteration in their nuclear levels. Pharmacological inhibitors of protein kinase C reversed the inhibitory effect of 5-HT on the promoter activity. Our data indicate that 5-HT suppresses the transcriptional activity of the NHE3 promoter and this effect may be mediated by PKC{alpha} and modulation of DNA-binding affinities of Sp1 and Sp3.},
doi = {10.1016/J.BBRC.2009.03.087},
url = {https://www.osti.gov/biblio/22199683}, journal = {Biochemical and Biophysical Research Communications},
issn = {0006-291X},
number = 3,
volume = 382,
place = {United States},
year = {Fri May 08 00:00:00 EDT 2009},
month = {Fri May 08 00:00:00 EDT 2009}
}