Tissue-nonspecific alkaline phosphatase is activated in enterocytes by oxidative stress via changes in glycosylation

Abstract

Oxidative stress causes a distinct increase in enterocyte AP activity together with cell toxicity via changes in the glycosylation of the enzyme that correspond to a shift in isotype within the tissue-nonspecific paradigm. We speculate that this may have physiological implication for gut defense.

Perinatal undernutrition alters intestinal alkaline phosphatase and its main transcription factors KLF4 and Cdx1 in adult offspring fed a high-fat diet

“…Serum AP analysis was conducted without and with levamisole (.1 M, tetramisole hydrochloride, reference L9756, Sigma, Saint-Quentin Fallavier, France) in order to evaluate the contribution of intestinal AP to total serum AP. Indeed, levamisole inhibits AP isoforms, except intestinal AP [30,31]. Serum fatty acids and triglycerides were analyzed as reported previously [15].…”

Fructooligosaccharides exert intestinal anti-inflammatory activity in the CD4+ CD62L+ T cell transfer model of colitis in C57BL/6J mice

“…This is based on the one hand on the observation that both AP enzyme activity and sensitivity to levamisole are decreased by FOS, consistent with reduced AP isoform shift in enterocytes, a known feature of epithelial cells under inflammatory conditions [33,35]. On the other hand, FOS augmented the expression of occludin, which is an integral plasma membrane protein that is important part of the tight junction complex in intestinal epithelial cells, among other tissues.…”

“…3a). Colonic AP activity, a marker of intestinal inflammation and epithelial stress [33][34][35], was also augmented threefold in group C, associated with a dramatic (over fivefold) increase in the sensitivity to the specific inhibitor levamisole in vitro (C vs. NC, p < 0.05, Fig. 3b, c).…”

“…The activities of MPO and AP were measured spectrophotometrically as described previously [32,33], and they are expressed as mU mg −1 protein. In addition, the sensitivity to the AP inhibitor levamisole was assessed, and it is expressed as a % of inhibition.…”

Intestinal inflammation and the enterocyte transportome

“…In addition to producing microlesions in the epithelial layer and causing a breach in its continuity, the enterocyte phenotype may change as a result of cellular stress and/or regulatory changes. For instance, we have described how epithelial cells may exhibit a change in the alkaline phosphatase isoform under these conditions, which may be involved in mucosal defence [8]. The occurrence of discontinuities in this barrier may conceivably favour fluid leakage to the lumen from the lamina propria, contributing to diarrhoea.…”