Helicobacter pylori-induced H,K-ATPase alpha-subunit gene repression is mediated by NF-kappaB p50 homodimer promoter binding

American Journal of Physiology. Gastrointestinal and Liver Physiology
Arindam SahaAdam J Smolka

Abstract

Infection of human gastric body mucosa by the gram-negative, microaerophilic bacterium Helicobacter pylori induces an inflammatory response and a transitory hypochlorhydria that progresses in approximately 2% of patients to atrophic gastritis, dysplasia, and gastric adenocarcinoma. We have previously shown that H. pylori infection of cultured gastric epithelial cells (AGS) represses the activity of the transfected alpha-subunit (HKalpha) promoter of H,K-ATPase, the parietal cell enzyme mediating acid secretion. However, the mechanistic details of H. pylori-mediated repression of HKalpha and ensuing hypochlorhydria are unknown. H. pylori is known to upregulate the transcription factor NF-kappaB through the ERK1/2 MAPK pathway. We identified NF-kappaB-binding regions in the HKalpha promoter and found that H. pylori inoculation of AGS cells increased NF-kappaB p50 binding to the transfected HKalpha promoter and repressed its transcriptional activity. Immunoblot and DNA-protein interaction studies showed that although active phosphorylated NF-kappaB p65 is present in H. pylori-infected AGS cells, an NF-kappaB p50/p65 heterodimeric complex fails to bind to the HKalpha promoter. Point mutations at -159 and -161 bp in the HKalpha prom...Continue Reading

References

Jun 1, 1992·Gastroenterology·M M Wolfe, D J Nompleggi
Oct 1, 1991·The American Journal of Physiology·J L WallaceL Parente
Jan 1, 1989·Annals of the New York Academy of Sciences·J G ForteJ M Wolosin
Apr 15, 1985·The Medical Journal of Australia·B J MarshallR J Glancy
Jan 1, 1995·Digestive Diseases and Sciences·J S HoffmanD R Cave
Feb 18, 1995·Lancet·H MiyajiM Kuriyama
May 10, 1994·Proceedings of the National Academy of Sciences of the United States of America·S TamuraM Futai
Nov 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·S TamuraM Futai
Jun 1, 1993·The Journal of Experimental Medicine·D PlaksinL Eisenbach
Nov 1, 1994·Comparative Biochemistry and Physiology. Part A, Physiology·G BjörnhagW von Engelhardt
Jul 1, 1997·Gastroenterology·E M El-OmarK E McColl
Aug 5, 1998·The American Journal of Physiology·O RégrignyI Lartaud-Idjouadiene
Nov 14, 1998·The American Journal of Physiology·W ScheppC Prinz
Apr 5, 2000·Baillière's Best Practice & Research. Clinical Gastroenterology·K E McCollE El-Omar
Jun 22, 2000·American Journal of Physiology. Gastrointestinal and Liver Physiology·M GöõzA J Smolka
Nov 4, 2000·Journal of Reproduction and Fertility·R B GilchristD T Armstrong
Feb 13, 2001·Clinical Microbiology and Infection : the Official Publication of the European Society of Clinical Microbiology and Infectious Diseases·F C BangeF Gunzer
Oct 6, 2001·Gastroenterology Clinics of North America·D E Katz, D N Taylor
Mar 21, 2002·Nature Reviews. Cancer·Richard M Peek, Martin J Blaser
Jul 18, 2002·American Journal of Physiology. Gastrointestinal and Liver Physiology·Bruno NeuChristian Prinz
Oct 10, 2002·American Journal of Physiology. Renal Physiology·Wenzheng Zhang, Bruce C Kone
Sep 17, 2004·Genes & Development·Matthew S Hayden, Sankar Ghosh

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Citations

Feb 5, 2011·Nature Reviews. Gastroenterology & Hepatology·Tom Luedde, Robert F Schwabe
Oct 12, 2010·Clinical Microbiology Reviews·Lydia E WroblewskiKeith T Wilson
Sep 6, 2008·American Journal of Physiology. Gastrointestinal and Liver Physiology·Arindam SahaAdam J Smolka
May 9, 2012·Journal of Gastroenterology·Adam J Smolka, Steffen Backert
Oct 21, 2016·Veterinary Research·Guangzhi ZhangFreddy Haesebrouck
Jan 6, 2009·Current Opinion in Gastroenterology·Mitchell L Schubert
Feb 8, 2014·American Journal of Physiology. Gastrointestinal and Liver Physiology·Yong-Mei ZhangAdam J Smolka
Jun 6, 2015·American Journal of Physiology. Gastrointestinal and Liver Physiology·Charles E HammondAdam J Smolka
Jul 28, 2015·Helicobacter·Carolina A SerranoPaul R Harris
Jul 27, 2021·Scandinavian Journal of Gastroenterology·Jun-Yan JiangMao-Xia Liu

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Atrophic Gastritis is a process where gastric glandular cells are lost and replaced with firbous tissues, as a result of chronic inflammation. Learn more about Atrophic Gastritis here.