title: Mitochondrial electron transport chain complex dysfunction in the colonic mucosa in ulcerative colitis.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Wellcome Trust Research Laboratory, Department of Gastrointestinal Sciences, Christian Medical College, Vellore, India.
authors.forename: Srikanth
authors.initials: S
authors.lastname: Santhanam
authors.forename: Subapriya
authors.initials: S
authors.lastname: Rajamanickam
authors.forename: Anjan
authors.initials: A
authors.lastname: Motamarry
authors.forename: Balakrishnan S
authors.initials: BS
authors.lastname: Ramakrishna
authors.forename: Jayakumar G
authors.initials: JG
authors.lastname: Amirtharaj
authors.forename: Anup
authors.initials: A
authors.lastname: Ramachandran
authors.forename: Anna
authors.initials: A
authors.lastname: Pulimood
authors.forename: Aparna
authors.initials: A
authors.lastname: Venkatraman
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D001706:Biopsy; D002478:Cells, Cultured; D003093:Colitis, Ulcerative / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D003106:Colon / Q000166:cytology* / Q000378:metabolism; D016264:Dextran Sulfate / Q000633:toxicity; D004579:Electron Transport / Q000502:physiology*; D045222:Electron Transport Chain Complex Proteins / Q000378:metabolism*; D042967:Electron Transport Complex I / Q000378:metabolism; D042963:Electron Transport Complex II / Q000378:metabolism; D014450:Electron Transport Complex III / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000378:metabolism; D005260:Female; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism / Q000473:pathology*; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D050050:Protein Carbonylation; D055815:Young Adult
chemical_list: D045222:Electron Transport Chain Complex Proteins; D009569:Nitric Oxide; D016264:Dextran Sulfate; D052247:Nitric Oxide Synthase Type II; D042963:Electron Transport Complex II; D003576:Electron Transport Complex IV; D042967:Electron Transport Complex I; D014450:Electron Transport Complex III