Role of Na+/H+ exchanger isoform-1 in human inflammatory bowel disease.
BACKGROUND
Na+/H+ exchanger (NHE) is responsible for a net uptake of sodium chloride and water from the gastrointestinal tract and maintains electrolyte and water homeostasis. However, its status in human inflammatory bowel disease such as ulcerative colitis (UC) and Crohn's disease (CD) remains poorly understood.


OBJECTIVE
To investigate the role of NHE-1 isoform in human CD and UC.


METHODS
Expression of NHE-1 protein and messenger ribonucleic acid and sodium pump activity were examined in the colonic biopsy samples taken from UC (n=11) and CD (n=13) patients using enhanced chemiluminescence-Western blot analysis, reverse transcription polymerase chain reaction and spectrophotometry. Subjects presenting with abdominal pain and endoscopically normal colon served as normal controls (n=11). Myeloperoxidase (MPO) activity and histology were performed to confirm tissue inflammation.


RESULTS
MPO activity increased significantly (P<0.05) in both UC and CD patients compared with the normal controls. Parallel to MPO activity profile, there was also a significantly higher infiltration of inflammatory cells in both cases. P-nitrophenylphosphatase activity, a marker of the sodium pump, remained unchanged in CD but increased significantly (P<0.05) in UC compared with the normal controls. On the contrary, the level of NHE-1 protein and messenger ribonucleic acid was significantly decreased (P<0.05) in both cases, whereas the internal control, a-actin remained unaltered.


CONCLUSIONS
These findings demonstrate a transcriptionally regulated suppression of NHE-1 in both UC and CD. This NHE-1 suppression may reduce an uptake of sodium chloride and water from the inflamed colonic lumen and thus contribute to diarrhea and neuromuscular alterations in these conditions.
Khan
Islam
I
Departmentof Biochemistry, Faculty of Medicine, Kuwait University, Kuwait. Islam@hsc.kuniv.edu.kw
Siddique
Iqbal
I
Al-Awadi
Farida M
FM
Mohan
Krishna
K
D000328:Adult; D003093:Colitis, Ulcerative / Q000378:metabolism* / Q000503:physiopathology; D003424:Crohn Disease / Q000378:metabolism* / Q000503:physiopathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009195:Peroxidase / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
D012333:RNA, Messenger; D017923:Sodium-Hydrogen Exchangers; C069139:growth factor-activatable Na-H exchanger NHE-1; D009195:Peroxidase; D000254:Sodium-Potassium-Exchanging ATPase