title: Tumor suppressor gene adenomatous polyposis coli downregulates intestinal transport.
abstract: Loss of function mutations of the tumor suppressor gene adenomatous polyposis coli (APC) underly the familial adenomatous polyposis. Mice carrying an inactivating mutation in the apc gene (apc (Min/+)) similarly develop intestinal polyposis. APC is effective at least in part by degrading β-catenin and lack of APC leads to markedly enhanced cellular β-catenin levels. β-Catenin has most recently been shown to upregulate the Na+/K+ ATPase. The present study, thus, explored the possibility that APC could influence intestinal transport. The abundance and localization of β-catenin were determined utilizing Western blotting and confocal microscopy, the activity of the electrogenic glucose carrier (SGLT1) was estimated from the glucose-induced current in jejunal segments utilizing Ussing chamber experiments and the Na+/H+ exchanger (NHE3) activity from Na+ -dependent re-alkalinization of cytosolic pH (ΔpH(i)) following an ammonium pulse employing BCECF fluorescence. As a result, β-catenin abundance in intestinal tissue was significantly higher in apc (Min/+) mice than in wild-type mice (apc (+/+)). The β-catenin protein was localized in the basolateral membrane. Both, the glucose-induced current and ΔpH(i) were significantly higher in apc (Min/+) mice than in apc (+/+) mice. In conclusion, intestinal electrogenic transport of glucose and intestinal Na+/H+ exchanger activity are both significantly enhanced in apc (Min/+) mice, pointing to a role of APC in the regulation of epithelial transport.
authors.affiliation: Department of Physiology, University of Tübingen, Gmelinstr. 5, 72076, Tübingen, Germany.
authors.forename: Rexhep
authors.initials: R
authors.lastname: Rexhepaj
authors.forename: Anand
authors.initials: A
authors.lastname: Rotte
authors.forename: Shuchen
authors.initials: S
authors.lastname: Gu
authors.forename: Diana
authors.initials: D
authors.lastname: Michael
authors.forename: Venkanna
authors.initials: V
authors.lastname: Pasham
authors.forename: Kan
authors.initials: K
authors.lastname: Wang
authors.forename: Daniela S
authors.initials: DS
authors.lastname: Kempe
authors.forename: Teresa F
authors.initials: TF
authors.lastname: Ackermann
authors.forename: Björn
authors.initials: B
authors.lastname: Brücher
authors.forename: Falko
authors.initials: F
authors.lastname: Fend
authors.forename: Michael
authors.initials: M
authors.lastname: Föller
authors.forename: Florian
authors.initials: F
authors.lastname: Lang
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000235:genetics; D015536:Down-Regulation; D017491:Genes, APC / Q000502:physiology*; D005947:Glucose / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007413:Intestinal Mucosa / Q000378:metabolism*; D051379:Mice; D051269:Sodium-Glucose Transporter 1 / Q000378:metabolism; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism*
chemical_list: C495675:Slc5a1 protein, mouse; C000613386:Slc9a3 protein, mouse; D051269:Sodium-Glucose Transporter 1; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers; D051176:beta Catenin; D005947:Glucose