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

Jan C. Becker, Nina Grosser, Christian Waltke, Stephanie Schulz, Kati Erdmann, Wolfram Domschke, Henning Schröder, Thorsten Pohle

Research output: Contribution to journalArticlepeer-review

65 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1014-1021
Number of pages8
JournalBiochemical and Biophysical Research Communications
Volume345
Issue number3
DOIs
StatePublished - Jul 7 2006

Keywords

  • Gastroprotection
  • Heme oxygenase-1
  • NSAID
  • Proton pump inhibitors
  • Reactive oxygen species
  • Vasoprotection

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