Document Detail

Preserved Na(+)/H(+) exchanger isoform 3 expression and localization, but decreased NHE3 function indicate regulatory sodium transport defect in ulcerative colitis.
MedLine Citation:
PMID:  20027604     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: A major causative factor of diarrhea in ulcerative colitis (UC) patients is the loss of Na(+) absorptive capacity of the inflamed colonic mucosa. Potential contributing mechanisms include reduced driving force for active transport, and impaired expression, mislocalization, or defective transport function of Na(+) absorptive proteins. We therefore studied the expression, brush border membrane (BBM) localization, and transport capacity of the major intestinal Na(+) absorptive protein, the Na(+)/H(+) exchanger isoform 3 (NHE3) in biopsies from UC patients. METHODS: In UC and control biopsies, inflammation was graded histologically, NHE3, tumor necrosis factor alpha (TNF-alpha), villin, as well as other housekeeping genes were analyzed by quantitative real-time polymerase chain reaction (PCR), BBM localization of NHE3 determined by immunohistochemistry, and confocal microscopy. Na(+) absorptive capacity was assessed by (22)Na(+) isotope fluxes and NHE3 transport activity measured microfluorometrically in BCECF-loaded surface colonocytes within isolated crypts. RESULTS: In mildly, moderately, and severely inflamed sigmoid colon of UC patients, neither NHE3 mRNA expression nor the abundance of NHE3 in the BBM was significantly altered compared to other structural components of the BBM. However, Na(+) absorption was strongly reduced by approximately 80% and acid-activated NHE3 transport activity was significantly decreased in the surface cells of sigmoid colonic crypts even in moderately inflamed mucosa. CONCLUSIONS: In the colonic mucosa of patients with active UC, NHE3 transport capacity was found significantly decreased despite correct NHE3 location and abundance in the brush border, independent of current treatment. These findings suggest functional NHE3 transport as a novel factor for inflammatory diarrhea in UC patients.
Sunil Yeruva; Klaudia Farkas; Jessica Hubricht; Katja Rode; Brigitte Riederer; Oliver Bachmann; Ayhan Cinar; Zoltán Rakonczay; Tamás Molnár; Ferenc Nagy; Jochen Wedemeyer; Michael Manns; Dirk Raddatz; Mark W Musch; Eugene B Chang; Péter Hegyi; Ursula Seidler
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Inflammatory bowel diseases     Volume:  16     ISSN:  1536-4844     ISO Abbreviation:  Inflamm. Bowel Dis.     Publication Date:  2010 Jul 
Date Detail:
Created Date:  2010-06-21     Completed Date:  2010-09-30     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9508162     Medline TA:  Inflamm Bowel Dis     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1149-61     Citation Subset:  IM    
Department of Gastroenterology, Hannover Medical School, Hannover, Germany.
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MeSH Terms
Blotting, Western
Colitis, Ulcerative / genetics,  metabolism*,  pathology
Colon / metabolism,  pathology
Immunoenzyme Techniques
Intestinal Absorption
Ion Transport
Microvilli / genetics,  metabolism*
RNA, Messenger / genetics
Reverse Transcriptase Polymerase Chain Reaction
Sodium / metabolism*
Sodium-Hydrogen Antiporter / genetics,  metabolism*
Tissue Distribution
Tumor Necrosis Factor-alpha / genetics,  metabolism
Reg. No./Substance:
0/RNA, Messenger; 0/Sodium-Hydrogen Antiporter; 0/Tumor Necrosis Factor-alpha; 0/sodium-hydrogen exchanger 3; 7440-23-5/Sodium

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