Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024523 (malabsorption)
 7,319 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bile acid malabsorption has been shown to be associated with diarrhea in cases such as ileal resection Crohn's disease of the ileum, and radiation enteritis. The mechanisms of bile acid-induced diarrhea are not fully understood. Although the induction of colonic chloride secretion in response to bile acids has been extensively investigated, to date the direct effect of bile acids on intestinal chloride absorption has not been well defined. Therefore, the current studies were undertaken to investigate the effect of bile acids on the apical Cl(-)/OH(-) exchange process utilizing Caco2 monolayers as an in vitro cellular model. Cl(-)/OH(-) exchange activity was measured as DIDS-sensitive pH gradient-driven (36)Cl uptake. The results are summarized as follows: (i) short-term exposure (20 min) of Caco2 cells to taurodeoxycholate (TDC; 200 microM) and glycochenodeoxycholate (GCDC; 200 microM) acids significantly inhibited apical Cl(-)/OH(-) exchange (by approximately 60-70%); (ii) the Ca(2+) chelator BAPTA-AM blocked the inhibition by TDC; (iii) the reduction in Cl(-)/OH(-) exchange by TDC was reversed by the PKC inhibitor, chelerythrine chloride; (iv) functional and inhibitor studies indicated that TDC induced inhibition of Cl(-)/OH(-) exchange was mediated via the activation of the PKC beta I isoform; (v) the effect of TDC on apical Cl(-)/OH(-) exchange was completely blocked by the PI3 kinase inhibitor LY294002 (5 microM); and (vi) the PKA inhibitor, RpcAMP, had no effect on TDC induced inhibition of Cl(-)/OH(-) exchange. In conclusion, our studies provide direct evidence for inhibition of human intestinal apical Cl(-)/OH(-) exchange activity by bile acids via Ca(2+)-, PI3 kinase-, and PKC beta I-dependent pathways in Caco2 cells.
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PMID:Taurodeoxycholate modulates apical Cl-/OH- exchange activity in Caco2 cells. 1738 13

Folate is an essential cofactor for normal cellular proliferation and tissue regeneration. Alcohol-associated folate deficiency is common, primarily due to intestinal malabsorption, the mechanism of which needs attention. The aim of the present study was to evaluate the regulatory events of folate transport in experimental alcohol ingestion. For this, male Wistar rats were fed 1 g/kg body weight/day ethanol (20% solution) orally for 3 months and folate transport was studied in isolated intestinal epithelial cells across the crypt-villus axis. The role of different signaling pathways in folate transport regulation was evaluated independently to that of reduced folate carrier (RFC) expression. The results showed that differentiated cells of villus possess high folate uptake activity as compared to mid villus and crypt base cells. During chronic ethanol ingestion, decrease in transport was observed all along the crypt-villus axis but was more pronounced at proliferating crypt base stem cells. Studying the effect of modulators of signaling pathways revealed the folate transport system to be under the regulation of cAMP-dependent protein kinase A (PKA), the activity of which was observed to decrease upon alcohol ingestion. In addition, protein kinase C might have a role in folate transport regulation during alcoholic conditions. The deregulation in the folate transport system was associated with a decrease in RFC expression, which may result in lower transport efficiency observed at absorptive surface in alcohol-fed rats. The study highlights the role that perturbed regulatory pathways and RFC expression play in the decreased folate transport at brush border surface during alcohol ingestion.
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PMID:Role of signaling pathways in the regulation of folate transport in ethanol-fed rats. 1860 15

Zinc is an important dietary factor that regulates intestinal amino acid and protein metabolism in animals. Recent work with the piglet, an established animal model for studying human infant nutrition, has shown that supplementing high levels of zinc oxide (ZnO) to the diet ameliorates weaning-associated intestinal injury and growth retardation. However, the underlying mechanisms are largely unknown. This study tested the hypothesis that zinc supplementation affects expression of proteins related to glutathione metabolism and oxidative stress in the gut. Using two-dimensional gel electrophoresis and mass spectrometry, we identified 22 up-regulated and 19 down-regulated protein spots in the jejunum of weanling piglets supplemented with ZnO (3,000 mg/kg Zn) compared with the control pigs (100 mg/kg Zn). These proteins are related to energy metabolism (increased level for succinyl-CoA transferase and decreased level for creatine kinase M-type); oxidative stress (decreased levels for 78 kDa glucose-regulated protein and glutathione-S-transferase-omega); and cell proliferation and apoptosis (increased levels for A-Raf-1 and calregulin). Consistent with the changes in protein expression, the ratio of reduced glutathione to oxidized glutathione was increased, whereas glutathione-S-transferase and glutathione peroxidase activities as well as the protein level of active caspase-3 were reduced in ZnO-supplemented piglets. Collectively, these results indicate that ZnO supplementation improves the redox state and prevents apoptosis in the jejunum of weaning piglets, thereby alleviating weaning-associated intestinal dysfunction and malabsorption of nutrients (including amino acids).
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PMID:Proteomic analysis reveals altered expression of proteins related to glutathione metabolism and apoptosis in the small intestine of zinc oxide-supplemented piglets. 1918 41