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Beyond gastric acid reduction: Proton pump inhibitors induce heme oxygenase-1 in gastric and endothelial cells

Abstract

Proton pump inhibitors (PPIs) have been demonstrated to prevent gastric mucosal injury by mechanisms independent of acid inhibition. Here we demonstrate that both omeprazole and lansoprazole protect human gastric epithelial and endothelial cells against oxidative stress. This effect was abrogated in the presence of the heme oxygenase-1 (HO-1) inhibitor ZnBG. Exposure to either PPI resulted in a strong induction of HO-1 expression on mRNA and protein level, and led to an increased activity of this enzyme. Expression of cyclooxygenase isoforms 1 and 2 remained unaffected, and COX-inhibitors did not antagonize HO-1 induction by PPIs. Our results suggest that the antioxidant defense protein HO-1 is a target of PPIs in both endothelial and gastric epithelial cells. HO-1 induction might account for the gastroprotective effects of PPIs independently of acid inhibition, especially in NSAID gastropathy. Moreover, our findings provide additional perspectives for a possible but yet unexplored use of PPIs in vasoprotection.
Authors:
Becker, Jan C; [1]  Grosser, Nina; [2]  Waltke, Christian; [1]  Schulz, Stephanie; [2]  Erdmann, Kati; [2]  Domschke, Wolfram; [1]  Schroeder, Henning; [2]  Pohle, Thorsten [1] 
  1. Department of Medicine B, University of Muenster, 48149 Muenster (Germany)
  2. Department of Pharmacology and Toxicology, School of Pharmacy, Martin Luther University, Halle-Wittenberg, 06099 Halle (Saale) (Germany)
Publication Date:
Jul 07, 2006
Product Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 345; Journal Issue: 3; Other Information: DOI: 10.1016/j.bbrc.2006.04.170; PII: S0006-291X(06)01014-X; Copyright (c) 2006 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Subject:
60 APPLIED LIFE SCIENCES; ANTIOXIDANTS; BIOLOGICAL STRESS; ENZYMES; GASTRIC ACID; HEME; INHIBITION; INJURIES
OSTI ID:
20854339
Country of Origin:
United States
Language:
English
Other Identifying Numbers:
Journal ID: ISSN 0006-291X; BBRCA9; TRN: US07R0114027329
Submitting Site:
INIS
Size:
page(s) 1014-1021
Announcement Date:
Apr 18, 2007

Citation Formats

Becker, Jan C, Grosser, Nina, Waltke, Christian, Schulz, Stephanie, Erdmann, Kati, Domschke, Wolfram, Schroeder, Henning, and Pohle, Thorsten. Beyond gastric acid reduction: Proton pump inhibitors induce heme oxygenase-1 in gastric and endothelial cells. United States: N. p., 2006. Web. doi:10.1016/j.bbrc.2006.04.170.
Becker, Jan C, Grosser, Nina, Waltke, Christian, Schulz, Stephanie, Erdmann, Kati, Domschke, Wolfram, Schroeder, Henning, & Pohle, Thorsten. Beyond gastric acid reduction: Proton pump inhibitors induce heme oxygenase-1 in gastric and endothelial cells. United States. doi:10.1016/j.bbrc.2006.04.170.
Becker, Jan C, Grosser, Nina, Waltke, Christian, Schulz, Stephanie, Erdmann, Kati, Domschke, Wolfram, Schroeder, Henning, and Pohle, Thorsten. 2006. "Beyond gastric acid reduction: Proton pump inhibitors induce heme oxygenase-1 in gastric and endothelial cells." United States. doi:10.1016/j.bbrc.2006.04.170. https://www.osti.gov/servlets/purl/10.1016/j.bbrc.2006.04.170.
@misc{etde_20854339,
title = {Beyond gastric acid reduction: Proton pump inhibitors induce heme oxygenase-1 in gastric and endothelial cells}
author = {Becker, Jan C, Grosser, Nina, Waltke, Christian, Schulz, Stephanie, Erdmann, Kati, Domschke, Wolfram, Schroeder, Henning, and Pohle, Thorsten}
abstractNote = {Proton pump inhibitors (PPIs) have been demonstrated to prevent gastric mucosal injury by mechanisms independent of acid inhibition. Here we demonstrate that both omeprazole and lansoprazole protect human gastric epithelial and endothelial cells against oxidative stress. This effect was abrogated in the presence of the heme oxygenase-1 (HO-1) inhibitor ZnBG. Exposure to either PPI resulted in a strong induction of HO-1 expression on mRNA and protein level, and led to an increased activity of this enzyme. Expression of cyclooxygenase isoforms 1 and 2 remained unaffected, and COX-inhibitors did not antagonize HO-1 induction by PPIs. Our results suggest that the antioxidant defense protein HO-1 is a target of PPIs in both endothelial and gastric epithelial cells. HO-1 induction might account for the gastroprotective effects of PPIs independently of acid inhibition, especially in NSAID gastropathy. Moreover, our findings provide additional perspectives for a possible but yet unexplored use of PPIs in vasoprotection.}
doi = {10.1016/j.bbrc.2006.04.170}
journal = {Biochemical and Biophysical Research Communications}
issue = {3}
volume = {345}
place = {United States}
year = {2006}
month = {Jul}
}