| Title | Molecular mechanism and functional consequences of lansoprazole-mediated heme oxygenase-1 induction. | | Author(s) | Schulz-Geske S, Erdmann K, Wong RJ, Stevenson DK, Schröder H, Grosser N | | Institution | Department of Pharmacology and Toxicology, School of Pharmacy, Martin Luther University Halle-Wittenberg, 06099 Halle, Germany. nina.grosser@pharmazie.uni-halle.de. | | Source | World J Gastroenterol 2009 Sep 21; 15(35):4392-401. | | Abstract | AIM: To investigate the molecular mechanism and functional consequences of heme oxygenase-1 (HO-1) activation by lansoprazole in endothelial cells and macrophages.
METHODS: Expression of HO-1 mRNA was analyzed by Northern blotting. Western blotting was used to determine the HO-1 and ferritin protein levels. NADPH-dependent reactive oxygen species (ROS) formation was measured with lucigenin-enhanced chemiluminescence. HO-1 promoter activity in mouse fibroblasts, stably transfected with a 15-kb HO-1 gene that drives expression of the reporter gene luciferase, was assessed using in vivo bioluminescence imaging.
RESULTS: Lansoprazole increased HO-1 mRNA levels in endothelial cells and HO-1 protein levels in macrophages. In addition, lansoprazole-induced ferritin protein levels in both cell systems. Moreover, induction of the antioxidant proteins HO-1 and ferritin by lansoprazole was followed by a decrease in NADPH-mediated ROS formation. The radical scavenging properties of lansoprazole were diminished in the presence of the HO inhibitor, chromium mesoporphyrin IX. Induction of HO-1 gene expression by lansoprazole was not related to oxidative stress or to the activation of the mitogen-activated protein kinase pathway. However, the phosphatidylinositol 3-kinase inhibitor LY294002 showed a concentration-dependent inhibition of HO-1 mRNA and promoter activity.
CONCLUSION: Activation of HO-1 and ferritin may account for the gastric protection of lansoprazole and is dependent on a pathway blocked by LY294002. | | Language | eng | | Pub Type(s) | Journal Article
| | PubMed ID | 19764090 |
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