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Tumor suppressor gene adenomatous polyposis coli downregulates intestinal transport

  • Ion Channels, Receptors and Transporters
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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 (ΔpHi) 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 ΔpHi 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.

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Acknowledgements

This work was supported by grants from DFG and BMBF (F.L.). The authors gratefully acknowledge the expert technical assistance by Elfriede Faber and the meticulous preparation of the manuscript by Lejla Subasic and Sari Ruebe.

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The authors have no conflict of interest to disclose.

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Authors and Affiliations

  1. Department of Physiology, University of Tübingen, Gmelinstr. 5, 72076, Tübingen, Germany

    Rexhep Rexhepaj, Anand Rotte, Shuchen Gu, Diana Michael, Venkanna Pasham, Kan Wang, Daniela S. Kempe, Teresa F. Ackermann, Michael Föller & Florian Lang

  2. Department of Surgery, University of Tübingen, Gmelinstr. 5, 72076, Tübingen, Germany

    Björn Brücher

  3. Institute of Pathology, University of Tübingen, Gmelinstr. 5, 72076, Tübingen, Germany

    Falko Fend

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  1. Rexhep Rexhepaj
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Correspondence to Florian Lang.

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Rexhep Rexhepaj and Anand Rotte shared first authorship.

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Rexhepaj, R., Rotte, A., Gu, S. et al. Tumor suppressor gene adenomatous polyposis coli downregulates intestinal transport. Pflugers Arch - Eur J Physiol 461, 527–536 (2011). https://doi.org/10.1007/s00424-011-0945-2

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