Rotte, Anand and Bhandaru, Madhuri and Foeller, Michael and Biswas, Raja and Mack, Andreas F. and Friedrich, Bjoern and Rexhepaj, Rexhep and Nasir, Omaima and Ackermann, Teresa F. and Boini, Krishna M. and Kunzelmann, Karl and Behrens, Jrgen and Lang, Florian (2009) APC Sensitive Gastric Acid Secretion. CELLULAR PHYSIOLOGY AND BIOCHEMISTRY, 23 (1-3). pp. 133-142. ISSN 1015-8987, 1421-9778
Full text not available from this repository. (Request a copy)Abstract
Adenomatous polyposis coli (APC) is a tumor suppressor gene inactivated in familial adenomatous polyposis and sporadic colorectal cancer. Mice carrying a loss-of-function mutation in the apc gene (apc(Min/+)) spontaneously develop gastrointestinal tumors. APC fosters degradation of beta-catenin, which in turn upregulates the serum-and glucocorticoid-inducible kinase SGK1. SGK1 stimulates KCNQ1, which is required for luminal K+ recycling and thus for gastric acid secretion. BCECF-fluorescence was utilized to determine gastric acid secretion in isolated gastric glands from apc(Min/+) mice and their wild type littermates (apc(+/+)). Western blotting was employed to analyse beta-catenin and SGK1 expression and immunohistochemistry to determine KCNQ1 protein abundance. beta-catenin and SGK1 expression were enhanced in apc(Min/+) mice. Cytosolic pH was similar in apc(Min/+) mice and apc(+/+) mice. Na+-independent pH recovery following an ammonium pulse (Delta pH/min), which reflects H+/K+ ATPase activity, was, however, significantly faster in apc(Min/+) mice than in apc(+/+) mice. In both genotypes Delta pH/min was abolished in the presence of H+/K+ ATPase inhibitor omeprazole (100 mu M). Treatment of apc(Min/+) and apc(+/+) mice with 5 mu M forskolin 15 minutes prior to the experiment or increase in local K+-concentrations to 35 mM (replacing Na+/NMDG) significantly increased Delta pH/min and abrogated the differences between genotypes. The increase of Delta pH/min in apc(Min/+) mice required SGK1, as it was abolished by additional knockout of SGK1 (apc(Min/+)/sgk1(-/-)). In conclusion, basal gastric acid secretion is significantly enhanced in apc(Min/+) mice, pointing to a role of APC in the regulation of gastric acid secretion. The effect of APC requires H+/K+ ATPase activity and is at least partially due to SGK1-dependent upregulation of KCNQ1. Copyright (C) 2009 S. Karger AG, Basel
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | INDUCIBLE KINASE SGK1; GLUCOCORTICOID-REGULATED KINASE; BETA-CATENIN; COLON-CARCINOMA; FACTOR NHERF2; SERUM; ACTIVATION; CELLS; PROTEIN; CANCER; H+ secretion; APC; Apc(min/+); Stomach; Omeprazole; Gastrin; Potassium; Forskolin |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Physiologie > Prof. Dr. Karl Kunzelmann |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 12 Oct 2020 04:49 |
| Last Modified: | 12 Oct 2020 04:49 |
| URI: | https://pred.uni-regensburg.de/id/eprint/29662 |
Actions (login required)
 |
View Item |
