Publication Type:

Journal Article

Source:

Cellular Physiology and Biochemistry, Karger Publishers, Volume 23, Number 1-3, p.133–142 (2009)

URL:

http://www.karger.com/Article/Abstract/204102#

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 (apcMin/+) spontaneously develop gastrointestinal tumors. APC fosters degradation of β-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 apcMin/+mice and their wild type littermates (apc+/+). Western blotting was employed to analyse β-catenin and SGK1 expression and immunohistochemistry to determine KCNQ1 protein abundance. β-catenin and SGK1 expression were enhanced in apcMin/+mice. Cytosolic pH was similar in apcMin/+ mice and apc+/+ mice. Na+-independent pH recovery following an ammonium pulse (ΔpH/min), which reflects H+/K+ ATPase activity, was, however, significantly faster in apcMin/+ mice than in apc+/+mice. In both genotypes ΔpH/min was abolished in the presence of H+/K+ ATPase inhibitor omeprazole (100 μM). Treatment of apcMin/+ and apc+/+mice with 5 μM forskolin 15 minutes prior to the experiment or increase in local K+-concentrations to 35 mM (replacing Na+/NMDG) significantly increased ΔpH/min and abrogated the differences between genotypes. The increase of ΔpH/min in apcMin/+mice required SGK1, as it was abolished by additional knockout of SGK1 (apcMin/+/sgk1-/-). In conclusion, basal gastric acid secretion is significantly enhanced in apcMin/+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.

Cite this Research Publication

A. Rotte, Bhandaru, M., Föller, M., Dr. Raja Biswas, Mack, A. F., Friedrich, B., Rexhepaj, R., Nasir, O., Ackermann, T. F., Boini, K. M., and , “APC sensitive gastric acid secretion”, Cellular Physiology and Biochemistry, vol. 23, pp. 133–142, 2009.

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