Localization of villin, a cytoskeletal protein specific to microvilli, in human ileum and colon and in colonic neoplasms

West, A. B.; Isaac, Catherine A.; Carboni, Joan M.; Morrow, Jon S.; Mooseker, Mark S.; Barwick, Kenneth W.

doi:10.1016/0016-5085(88)90421-0

Cited by 95 publications

(62 citation statements)

References 34 publications

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“…Our studies suggest that Hh pathway activity is lost from colon cancer cells owing to the activation of Wnt signaling in these cells. Notably, the redistribution of Villin from the apical membrane to the cytoplasm, loss of expression of brush border enzymes and inappropriate induction of ITF expression in the enterocyte lineage that we observed in cyclopamine-treated rats are all aspects of loss of differentiation that are also observed during colorectal carcinogenesis 6,18 . Thus, the loss of Ihh expression secondary to the Wnt-activating APC mutation may have a role in the development of dysplasia in response to the APC mutation.…”

mentioning

confidence: 68%

Indian Hedgehog is an antagonist of Wnt signaling in colonic epithelial cell differentiation

et al. 2004

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mentioning

confidence: 68%

Indian Hedgehog is an antagonist of Wnt signaling in colonic epithelial cell differentiation

et al. 2004

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“…The AP activity in slices remained constant up to 24 h. In addition, the increase of enzyme activity in medium indicates that the cells are capable of de novo synthesis of AP during incubation. In addition, villin expression was evaluated during incubation, as it is commonly considered the housekeeping gene for enterocytes (Engman et al, 2001) in which it is exclusively expressed (West et al, 1988). Assuming that 1) the protein content is a measure for the amount of tissue in the slice, 2) the expression of villin is directly correlated to the amount of enterocytes in the slice, and taking into account the fact that 3) GAPDH remained constant in both small intestinal and colon slices up to 24 h, our results indicate that in colon slices no cells are lost up to 24 h, because all parameters that were tested remained constant (villin and GAPDH expression, the amount of protein per slice, and ATP and activity levels).…”

Section: Discussionmentioning

confidence: 99%

Induction of Phase I and II Drug Metabolism in Rat Small Intestine and Colon in Vitro

et al. 2007

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ABSTRACT:The aim of this study was to evaluate drug metabolism in rat small intestinal and colon precision-cut slices during 24 h of incubation and the applicability of these slices for enzyme induction studies. Various parameters were evaluated: intracellular levels of ATP (general viability marker), alkaline phosphatase activity (specific epithelial marker), villin expression (specific epithelial marker), and metabolic rates of 7-ethoxycoumarin (CYP1A), testosterone (CYP3A and CYP2B), and 7-hydroxycoumarin (glucuronide and sulfate conjugation) conversions. ATP and villin remained constant up to, respectively, 5 and 8 h in small intestine and up to 24 h in colon. The metabolic rate remained constant in small intestinal slices up to 8 h and decreased afterward to 24 to 92%, depending on the substrate studied. The inducibility of metabolism in small intestinal and colon slices was tested with several inducers at various concentrations and incubation times. The following inducers were used: 3-methylcholanthrene, ␤-naphthoflavone, indirubin, and tertbutylhydroquinone (aryl hydrocarbon receptor ligands), dexamethasone (glucocorticoid receptor/pregnane X receptor ligand) and phenobarbital (constitutive androstane receptor ligand). After incubation with inducers, metabolic rates were evaluated with 7-ethoxycoumarin and testosterone (phase I) and 7-hydroxycoumarin (phase II) as substrate. All inducers elevated the metabolic rates consistent with the available published in vivo induction data. Induction of enzyme activity was already detectable after 5 h (small intestine) and after 8 h (colon) for 3-methylcholanthrene and ␤-naphthoflavone and was clearly detectable for all tested inducers after 24 h (up to 20-fold compared with noninduced controls). In conclusion, small intestinal and colon precision-cut slices are useful for metabolism and enzyme induction studies.

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“…Because Bcrp is localized only in epithelial cells of the intestine (Maliepaard et al, 2001), the protein expression of Bcrp was normalized by that of villin to correct for intersample variations in the enrichment of epithelial cells. Villin was chosen because it is specifically expressed in epithelial cells, and its use as a correction marker was established in earlier reports (West et al, 1988;Lown et al, 1997). Bcrp/villin ratios represent the protein levels of Bcrp in epithelial cells.…”

Section: Resultsmentioning

confidence: 99%

Regional Expression and Activity of Breast Cancer Resistance Protein (Bcrp/Abcg2) in Mouse Intestine: Overlapping Distribution with Sulfotransferases

Enokizono

Kusuhara²,

Sugiyama³

2007

Drug Metab Dispos

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ABSTRACT:Breast cancer resistance protein (Bcrp/Abcg2) is a member of the ATP-binding cassette transporter family with the ability to transport a variety of sulfate conjugates. In the present study, the regional expression and activity of Bcrp and sulfotransferases (SULTs/Sults) were investigated in mouse intestine. Western blotting analysis revealed the highest expression of Bcrp in the ileum over the duodenum, jejunum, and colon. Functional analysis of Bcrp was performed in everted intestinal sacs using 4-methylumbelliferone (4MU). The mucosal secretion clearance of 4MU sulfate formed in the enterocytes was markedly reduced in the jejunum, ileum, and colon of Bcrp (؊/؊) mice in comparison with wild-type mice, whereas a slight and nonsignificant reduction was observed in the duodenum. The reduction in the mucosal secretion clearance was most marked in the ileum followed by the colon and jejunum. In addition, the mucosal secretion clearance of minoxidil sulfate, an active metabolite of minoxidil, was also significantly reduced in the intestine of Bcrp (؊/؊) mice. The sulfation activity of 4MU was higher in the colon than in the small intestine where glucuronidation activity was somewhat higher than the sulfation activity. Real-time polymerase chain reaction analysis showed that the expression of sulfotransferases, such as Sult1a1/2, Sult1b1, and Sult1d1, was also highest in the colon. These results suggest that Bcrp activity is higher in the mid to lower intestine and that the cooperation of Bcrp and SULT provides an important detoxification pathway, particularly in the colon.

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Localization of villin, a cytoskeletal protein specific to microvilli, in human ileum and colon and in colonic neoplasms

Cited by 95 publications

References 34 publications

Indian Hedgehog is an antagonist of Wnt signaling in colonic epithelial cell differentiation

Indian Hedgehog is an antagonist of Wnt signaling in colonic epithelial cell differentiation

Induction of Phase I and II Drug Metabolism in Rat Small Intestine and Colon in Vitro

Regional Expression and Activity of Breast Cancer Resistance Protein (Bcrp/Abcg2) in Mouse Intestine: Overlapping Distribution with Sulfotransferases

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