Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.2.1.26 (invertase)
 4,927 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Differentiated villus intestinal epithelial cells express globotriaosylceramide, the Shiga-like toxin 1 (SLT-1) receptor, and are sensitive to toxin-mediated cytotoxicity, whereas undifferentiated crypt cells neither express Gb3 nor respond to toxin. To investigate if SLT-1 receptors are maturationally regulated in human intestinal cells, we examined the effect of butyrate, a known transcriptional regulator of differentiation genes in many cell types, using cultured colonic cancer-derived epithelial cell lines. Exposure to butyrate increased villus cell marker enzymes such as alkaline phosphatase, sucrase, and lactase, expression of toxin receptors, and sensitivity to SLT-1 in villus-like CaCo-2A and HT-29 cells. These effects were reversibly inhibited by preincubation of CaCo-2A cells with actinomycin D or cycloheximide. Butyrate-treated CaCo-2A cells unable to bind fluoresceinated SLT-1 B subunit were undifferentiated as assessed by alkaline phosphatase activity. HT-29 cells induced to differentiate by another signal, glucose deprivation, upregulated receptor content and response to toxin. Crypt-like T-84 cells responded to butyrate with a modest increase in alkaline phosphatase and toxin binding, but no induction of sucrase or lactase, and no change in sensitivity to toxin. The results demonstrate that expression of SLT-1 toxin receptors and toxin sensitivity are coregulated with cellular differentiation in cultured intestinal cells.
 ...
PMID:Maturational regulation of globotriaosylceramide, the Shiga-like toxin 1 receptor, in cultured human gut epithelial cells. 765 8

The activities of lactase, sucrase and alkaline phosphatase (AP) were studied in intestinal brush border membranes of control and toxin-treated rabbits. Purified Shiga toxin (Stx) exposure to ileal mucosa inhibited activities of brush border enzymes by 50%. Kinetic analysis revealed that the observed decrease in BBM enzyme activities was due to reduced V(max) with no change in the affinity constants of the systems. The observed changes in enzyme activities were corroborated by Western Blot analysis of lactase, sucrase and AP. The mRNA levels encoding sucrase and lactase proteins in control and Shiga toxin-treated rabbit ileum did not show any change in the rabbit ileum. Histopathological analysis showed short, blunt villi with increased number of inflammatory cells in the lamina propria and extrusion of cells in to the lumen of Stx-treated rabbit ileum. The present findings suggest that Shiga toxin act by inhibiting protein synthesis of these brush border functional proteins beyond their transcriptional level and by the direct damage to intestinal epithelium, which could be implicated in the pathogenesis of diarrhea.
 ...
PMID:Shiga toxin exposure modulates intestinal brush border membrane functional proteins in rabbit ileum. 1644 89