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 ...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 usingin vivo bioluminescence imaging. RESULTS： Lansoprazole levels in endothelial cells increased HO-1 mRNA 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.展开更多
In the present paper the increasing difficulty of diag-nosis of Zollinger-Ellison syndrome (ZES) due to issues raised in two recent papers is discussed. These issues involve the difficulty and need to withdraw patient...In the present paper the increasing difficulty of diag-nosis of Zollinger-Ellison syndrome (ZES) due to issues raised in two recent papers is discussed. These issues involve the difficulty and need to withdraw patients suspected of ZES from treatment with Proton Pump Inhibitors (omeprazole, esomeprazole, lansoprazole, rabeprazole, pantoprazole) and the unreliability of many gastrin radioimmunoassays. The clinical context of each of these important issues is reviewed and the conclusions in these articles commented from the per-spective of clinical management.展开更多
基金Supported by The German Academic Exchange Program(DAAD,S.S.G.)
文摘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 usingin vivo bioluminescence imaging. RESULTS： Lansoprazole levels in endothelial cells increased HO-1 mRNA 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.
文摘In the present paper the increasing difficulty of diag-nosis of Zollinger-Ellison syndrome (ZES) due to issues raised in two recent papers is discussed. These issues involve the difficulty and need to withdraw patients suspected of ZES from treatment with Proton Pump Inhibitors (omeprazole, esomeprazole, lansoprazole, rabeprazole, pantoprazole) and the unreliability of many gastrin radioimmunoassays. The clinical context of each of these important issues is reviewed and the conclusions in these articles commented from the per-spective of clinical management.
