Becker Jan C, Grosser Nina, Waltke Christian, Schulz Stephanie, Erdmann Kati, Domschke Wolfram, Schröder Henning, Pohle Thorsten
Department of Medicine B, University of Muenster, 48149 Muenster, Germany.
Biochem Biophys Res Commun. 2006 Jul 7;345(3):1014-21. doi: 10.1016/j.bbrc.2006.04.170. Epub 2006 May 6.
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.
质子泵抑制剂（PPIs）已被证明可通过独立于酸抑制的机制预防胃黏膜损伤。在此，我们证明奥美拉唑和兰索拉唑均可保护人胃上皮细胞和内皮细胞免受氧化应激。在血红素加氧酶-1（HO-1）抑制剂ZnBG存在的情况下，这种效应被消除。暴露于任何一种PPI均可导致HO-1在mRNA和蛋白质水平上的强烈诱导，并导致该酶活性增加。环氧合酶同工型1和2的表达未受影响，并且COX抑制剂不会拮抗PPI对HO-1的诱导。我们的结果表明，抗氧化防御蛋白HO-1是PPI在内皮细胞和胃上皮细胞中的作用靶点。HO-1的诱导可能是PPI独立于酸抑制的胃保护作用的原因，尤其是在非甾体抗炎药胃病中。此外，我们的研究结果为PPI在血管保护中可能但尚未探索的用途提供了额外的视角。
