RRC ID 42650
著者 Becker JC, Grosser N, Waltke C, Schulz S, Erdmann K, Domschke W, Schröder H, Pohle T.
タイトル Beyond gastric acid reduction: proton pump inhibitors induce heme oxygenase-1 in gastric and endothelial cells.
ジャーナル Biochem Biophys Res Commun
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.
巻・号 345(3)
ページ 1014-21
公開日 2006-7-7
DOI 10.1016/j.bbrc.2006.04.170
PII S0006-291X(06)01014-X
PMID 16712795
MeSH 2-Pyridinylmethylsulfinylbenzimidazoles Animals Cell Line, Tumor Cyclooxygenase 1 / chemistry Deuteroporphyrins / pharmacology Endothelial Cells / metabolism* Enzyme Inhibitors / pharmacology Gastric Acid / metabolism* Gastric Mucosa / metabolism* Heme Oxygenase-1 / antagonists & inhibitors Heme Oxygenase-1 / biosynthesis* Humans Lansoprazole Omeprazole / analogs & derivatives Omeprazole / pharmacology Oxidative Stress Rats
IF 2.985
引用数 53
WOS 分野 BIOPHYSICS BIOCHEMISTRY & MOLECULAR BIOLOGY
リソース情報
ヒト・動物細胞 RGM1(RCB0876)