Lactobacillus acidophilus upregulates intestinal NHE3 expression and function

Varsha Singh, Geetu Raheja, Alip Borthakur, Anoop Kumar, Ravinder K. Gill, Anas Alakkam, Jaleh Malakooti, Pradeep K. Dudeja

Research output: Contribution to journalArticle

Abstract

A major mechanism of electroneutral NaCl absorption in the human ileum and colon involves coupling of Na+/H+ and Cl-/HCO3- exchangers. Disturbances in these mechanisms have been implicated in diarrheal conditions. Probiotics such as Lactobacillus have been indicated to be beneficial in the management of gastrointestinal disorders, including diarrhea. However, the molecular mechanisms underlying antidiarrheal effects of probiotics have not been fully understood. We have previously demonstrated Lactobacillus acidophilus (LA) to stimulate Cl-/HCO3- exchange activity via an increase in the surface levels and expression of the Cl-/HCO3- exchanger DRA in vitro and in vivo. However, the effects of LA on NHE3, the Na+/H+ exchanger involved in the coupled electroneutral NaCl absorption, are not known. Current studies were, therefore, undertaken to investigate the effects of LA on the function and expression of NHE3 and to determine the mechanisms involved. Treatment of Caco2 cells with LA or its conditioned culture supernatant (CS) for 8-24 h resulted in a significant increase in Na+/H+ exchange activity, mRNA, and protein levels of NHE3. LA-CS upregulation of NHE3 function and expression was also observed in SK-CO15 cells, a human colonic adenocarcinoma cell line. Additionally, LA treatment increased NHE3 promoter activity, suggesting involvement of transcriptional mechanisms. In vivo, mice gavaged with live LA showed significant increase in NHE3 mRNA and protein expression in the ileum and colonic regions. In conclusion, LA-induced increase in NHE3 expression may contribute to the upregulation of intestinal electrolyte absorption and might underlie the potential antidiarrheal effects of probiotics.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume303
Issue number12
DOIs
StatePublished - Dec 15 2012
Externally publishedYes

Fingerprint

Lactobacillus acidophilus
Up-Regulation
Probiotics
Chloride-Bicarbonate Antiporters
Antidiarrheals
Ileum
Messenger RNA
Sodium-Hydrogen Antiporter
Intestinal Absorption
Lactobacillus
Electrolytes
Diarrhea
Colon
Proteins
Adenocarcinoma
Cell Line

Keywords

  • Diarrhea
  • Intestinal sodium absorption
  • NHE3
  • Probiotics

ASJC Scopus subject areas

  • Gastroenterology
  • Physiology (medical)
  • Physiology
  • Hepatology

Cite this

Lactobacillus acidophilus upregulates intestinal NHE3 expression and function. / Singh, Varsha; Raheja, Geetu; Borthakur, Alip; Kumar, Anoop; Gill, Ravinder K.; Alakkam, Anas; Malakooti, Jaleh; Dudeja, Pradeep K.

In: American Journal of Physiology - Gastrointestinal and Liver Physiology, Vol. 303, No. 12, 15.12.2012.

Research output: Contribution to journalArticle

Singh, Varsha ; Raheja, Geetu ; Borthakur, Alip ; Kumar, Anoop ; Gill, Ravinder K. ; Alakkam, Anas ; Malakooti, Jaleh ; Dudeja, Pradeep K. / Lactobacillus acidophilus upregulates intestinal NHE3 expression and function. In: American Journal of Physiology - Gastrointestinal and Liver Physiology. 2012 ; Vol. 303, No. 12.
@article{b5264375559541d0b0f7d96123637ac7,
title = "Lactobacillus acidophilus upregulates intestinal NHE3 expression and function",
abstract = "A major mechanism of electroneutral NaCl absorption in the human ileum and colon involves coupling of Na+/H+ and Cl-/HCO3- exchangers. Disturbances in these mechanisms have been implicated in diarrheal conditions. Probiotics such as Lactobacillus have been indicated to be beneficial in the management of gastrointestinal disorders, including diarrhea. However, the molecular mechanisms underlying antidiarrheal effects of probiotics have not been fully understood. We have previously demonstrated Lactobacillus acidophilus (LA) to stimulate Cl-/HCO3- exchange activity via an increase in the surface levels and expression of the Cl-/HCO3- exchanger DRA in vitro and in vivo. However, the effects of LA on NHE3, the Na+/H+ exchanger involved in the coupled electroneutral NaCl absorption, are not known. Current studies were, therefore, undertaken to investigate the effects of LA on the function and expression of NHE3 and to determine the mechanisms involved. Treatment of Caco2 cells with LA or its conditioned culture supernatant (CS) for 8-24 h resulted in a significant increase in Na+/H+ exchange activity, mRNA, and protein levels of NHE3. LA-CS upregulation of NHE3 function and expression was also observed in SK-CO15 cells, a human colonic adenocarcinoma cell line. Additionally, LA treatment increased NHE3 promoter activity, suggesting involvement of transcriptional mechanisms. In vivo, mice gavaged with live LA showed significant increase in NHE3 mRNA and protein expression in the ileum and colonic regions. In conclusion, LA-induced increase in NHE3 expression may contribute to the upregulation of intestinal electrolyte absorption and might underlie the potential antidiarrheal effects of probiotics.",
keywords = "Diarrhea, Intestinal sodium absorption, NHE3, Probiotics",
author = "Varsha Singh and Geetu Raheja and Alip Borthakur and Anoop Kumar and Gill, {Ravinder K.} and Anas Alakkam and Jaleh Malakooti and Dudeja, {Pradeep K.}",
year = "2012",
month = "12",
day = "15",
doi = "10.1152/ajpgi.00345.2012",
language = "English (US)",
volume = "303",
journal = "American Journal of Physiology",
issn = "0363-6135",
publisher = "American Physiological Society",
number = "12",

}

TY - JOUR

T1 - Lactobacillus acidophilus upregulates intestinal NHE3 expression and function

AU - Singh, Varsha

AU - Raheja, Geetu

AU - Borthakur, Alip

AU - Kumar, Anoop

AU - Gill, Ravinder K.

AU - Alakkam, Anas

AU - Malakooti, Jaleh

AU - Dudeja, Pradeep K.

PY - 2012/12/15

Y1 - 2012/12/15

N2 - A major mechanism of electroneutral NaCl absorption in the human ileum and colon involves coupling of Na+/H+ and Cl-/HCO3- exchangers. Disturbances in these mechanisms have been implicated in diarrheal conditions. Probiotics such as Lactobacillus have been indicated to be beneficial in the management of gastrointestinal disorders, including diarrhea. However, the molecular mechanisms underlying antidiarrheal effects of probiotics have not been fully understood. We have previously demonstrated Lactobacillus acidophilus (LA) to stimulate Cl-/HCO3- exchange activity via an increase in the surface levels and expression of the Cl-/HCO3- exchanger DRA in vitro and in vivo. However, the effects of LA on NHE3, the Na+/H+ exchanger involved in the coupled electroneutral NaCl absorption, are not known. Current studies were, therefore, undertaken to investigate the effects of LA on the function and expression of NHE3 and to determine the mechanisms involved. Treatment of Caco2 cells with LA or its conditioned culture supernatant (CS) for 8-24 h resulted in a significant increase in Na+/H+ exchange activity, mRNA, and protein levels of NHE3. LA-CS upregulation of NHE3 function and expression was also observed in SK-CO15 cells, a human colonic adenocarcinoma cell line. Additionally, LA treatment increased NHE3 promoter activity, suggesting involvement of transcriptional mechanisms. In vivo, mice gavaged with live LA showed significant increase in NHE3 mRNA and protein expression in the ileum and colonic regions. In conclusion, LA-induced increase in NHE3 expression may contribute to the upregulation of intestinal electrolyte absorption and might underlie the potential antidiarrheal effects of probiotics.

AB - A major mechanism of electroneutral NaCl absorption in the human ileum and colon involves coupling of Na+/H+ and Cl-/HCO3- exchangers. Disturbances in these mechanisms have been implicated in diarrheal conditions. Probiotics such as Lactobacillus have been indicated to be beneficial in the management of gastrointestinal disorders, including diarrhea. However, the molecular mechanisms underlying antidiarrheal effects of probiotics have not been fully understood. We have previously demonstrated Lactobacillus acidophilus (LA) to stimulate Cl-/HCO3- exchange activity via an increase in the surface levels and expression of the Cl-/HCO3- exchanger DRA in vitro and in vivo. However, the effects of LA on NHE3, the Na+/H+ exchanger involved in the coupled electroneutral NaCl absorption, are not known. Current studies were, therefore, undertaken to investigate the effects of LA on the function and expression of NHE3 and to determine the mechanisms involved. Treatment of Caco2 cells with LA or its conditioned culture supernatant (CS) for 8-24 h resulted in a significant increase in Na+/H+ exchange activity, mRNA, and protein levels of NHE3. LA-CS upregulation of NHE3 function and expression was also observed in SK-CO15 cells, a human colonic adenocarcinoma cell line. Additionally, LA treatment increased NHE3 promoter activity, suggesting involvement of transcriptional mechanisms. In vivo, mice gavaged with live LA showed significant increase in NHE3 mRNA and protein expression in the ileum and colonic regions. In conclusion, LA-induced increase in NHE3 expression may contribute to the upregulation of intestinal electrolyte absorption and might underlie the potential antidiarrheal effects of probiotics.

KW - Diarrhea

KW - Intestinal sodium absorption

KW - NHE3

KW - Probiotics

UR - http://www.scopus.com/inward/record.url?scp=84871335710&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84871335710&partnerID=8YFLogxK

U2 - 10.1152/ajpgi.00345.2012

DO - 10.1152/ajpgi.00345.2012

M3 - Article

VL - 303

JO - American Journal of Physiology

JF - American Journal of Physiology

SN - 0363-6135

IS - 12

ER -