Mitochondrial electron transport chain complex dysfunction in the colonic mucosa in ulcerative colitis
Article first published online: 28 FEB 2012
Copyright © 2012 Crohn's & Colitis Foundation of America, Inc.
Inflammatory Bowel Diseases
Volume 18, Issue 11, pages 2158–2168, November 2012
How to Cite
Santhanam, S., Rajamanickam, S., Motamarry, A., Ramakrishna, B. S., Amirtharaj, J. G., Ramachandran, A., Pulimood, A. and Venkatraman, A. (2012), Mitochondrial electron transport chain complex dysfunction in the colonic mucosa in ulcerative colitis. Inflamm Bowel Dis, 18: 2158–2168. doi: 10.1002/ibd.22926
- Issue published online: 15 OCT 2012
- Article first published online: 28 FEB 2012
- Manuscript Accepted: 1 FEB 2012
- Manuscript Received: 16 JAN 2012
- Council for Scientific and Industrial Research, New Delhi, India. Grant Number: 27(0145)/05/EMR-II
- ulcerative colitis;
- colonic mucosa;
- electron transport chain;
- mitochondrial dysfunction;
- nitric oxide
Ulcerative colitis (UC) is characterized by an energy deficiency state of the colonic epithelium. This study evaluated mitochondrial electron transport chain (ETC) complex activity in normal and disease mucosa in patients with UC. Alterations in ETC complexes were also investigated in experimental colitis in mice.
Biopsies were obtained from macroscopically normal and diseased colonic mucosa of 43 patients with UC and 35 controls undergoing screening colonoscopy and ETC complex activity was assayed biochemically. ETC complex activities were also assayed in colonic epithelial cells isolated from Swiss albino mice with dextran sodium sulfate (DSS)-induced colitis at various stages of induction of colitis. Mucosal nitrite levels and protein carbonyl content were determined.
The activity of Complex II was significantly decreased in colonic biopsies from UC patients compared with controls, while activities of other mitochondrial complex were normal. Complex II activity was equally decreased in diseased and normal mucosa in UC; the degree of reduction did not correlate with clinical, endoscopic, or histological grading of disease activity. In DSS-fed mice, a reduction in activity of Complex IV and Complex II was observed. Activity of other complex was not affected. Administration of aminoguanidine, an inducible nitric oxide synthase (iNOS) inhibitor, attenuated all parameters of colitis as well as the reductions in Complex IV and Complex II activity.
Reduction in Complex II activity appears to be a specific change in UC, present in quiescent and active disease. Mitochondrial complex dysfunction occurs in DSS colitis in mice and appears to be mediated by nitric oxide. (Inflamm Bowel Dis 2012;)