Mitochondrial respiratory chain in the colonic mucosal of patients with ulcerative colitis

Abstract

Ulcerative colitis (UC) is a chronic inflammatory disease of the large bowel. Its pathogenesis remains unclear, but it appears to result from a deregulated immune response, with infiltration of leukocytes into the mucosal interstitium. Several studies link oxidative stress and mitochondrial dysfunction to the pathogenesis of UC. Thus, the aim of this study was to evaluate the activities of mitochondrial respiratory chain complexes in the colonic mucosal of UC patients. Colonic biopsies were obtained from UC patients (n = 13). The control specimens were taken from patients without any history of inflammatory bowel disease (n = 8). Colon mucosal was removed by colonoscopy and homogenized. Mitochondrial respiratory chain complexes activities were then measured. Our results showed that the activity of complex I was not altered in UC patients, when compared to the control group. On the other hand, complexes II, III, and IV were decreased around 50-60% in the colonic mucosal of UC patients. Based on the present findings, we hypothesize that mitochondrial dysfunction may play a role in pathogenesis of UC.

Peroxisome Proliferator-activated Receptor-γ Coactivator 1-α (PGC1α) Protects against Experimental Murine Colitis

“…jected to experimental colitis (11)(12)(13). With changes appearing in inflamed and non-inflamed segments of bowel, these data may suggest underlying changes in mitochondrial function, which may contribute to not only the pathogenesis of colitis, but also to the susceptibility to disease.…”

“…Intestinal tissue from BALB/c mice subjected to TNBS colitis was similarly analyzed for DHE staining, and an increase in superoxide ions is seen in mice with colitis (D, panels i and ii). *, p Յ 0.05. ting of human colitis as well as murine DSS colitis (11,12). To assess evidence of mitochondrial dysfunction in our model, we subjected C57BL/6 wild-type mice to 3% DSS for 7 days.…”

Preventive Effects of Spirogyra neglecta and a Polysaccharide Extract against Dextran Sodium Sulfate Induced Colitis in Mice

“…Moreover, proteome analysis indicated that DSS application led to down-regulation of COX5A, which is a subunit of cytochrome c oxidase (complex IV). Previously, Sifroni et al reported activities of mitochondrial respiratory chain enzymes such as complex II-IV to be decreased in UC patients (Sifroni et al, 2010). Moreover, there are several studies providing evidence of ROS production in UC patients (Nishikawa et al, 2005;Rana et al, 2014) and in chemical-induced colitis using animal models (Damiani et al, 2007).…”

“…The pathogenesis of UC is multifactorial and many aspects remain unclear. Several studies reported that mitochondrial dysfunction may play an important role in the pathogenesis of UC (Hsieh et al, 2006;Sifroni et al, 2010). Dysfunction of mitochondria usually leads to reduction in energy supply, increased ROS and induction of apoptotic cell death (Hsieh et al, 2006).…”

Prohibitin 1 modulates mitochondrial function of Stat3

“…It is well-established that IEC mitochondrial dysfunction is associated with IBD, as demonstrated by reduced ATP levels, activated mitochondrial unfolded-protein response, reduced activities of ETC complexes, and increased mitochondrial-derived ROS [5, 13, 40-42]. Ultrastructural abnormalities of epithelial cell mitochondria including swelling and irregular and/or dissolved cristae indicative of impaired function are thought to be an early event in the onset of mucosal inflammation since they are evident prior to endoscopic or histologic inflammation [8, 9].…”