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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: OBJECTIVE, RESULTS. Meshes: Cells, Cultured, Deoxyribonuclease I, Endothelium, Vascular, Enzyme Induction, Gene Expression Regulation, Enzymologic, Half-Life, Heme Oxygenase (Decyclizing), Heme Oxygenase-1, Humans, Linoleic Acids, Lipid Metabolism, Lipid Peroxides, Membrane Proteins, Mitogen-Activated Protein Kinases, Oxidation-Reduction, RNA, Messenger, Reactive Oxygen Species, Signal Transduction.
user
Does a cis-acting region regulate oxidized lipid-mediated induction of the human heme oxygenase-1 gene in endothelial cells? Context: Several proatherogenic agents including oxidized LDL and its major component, 13-hydroperoxyoctadecadienoic acid (13-HPODE), upregulate heme oxygenase-1 (HO-1). Our previous studies have demonstrated that 13-HPODE-mediated HO-1 induction occurs via transcriptional mechanisms. The purpose of this study was to evaluate the molecular regulation and identify the signaling pathways involved in 13-HPODE-mediated HO-1 induction in human aortic endothelial cells. The half-life of HO-1 mRNA after stimulation with 13-HPODE was approximately 1.8 hours. Antioxidants such as N-acetylcysteine, iron chelation with deferoxamine mesylate, and protein kinase C inhibition with Gö6976 blocked HO-1 induction. Using promoter constructs up to 9.1 kb, no significant reporter activity was observed in response to 13-HPODE. A 13-HPODE-inducible DNase I hypersensitive site was identified that maps to a region approximately 10 to 11 kb from the transcription start site of the human HO-1 gene. Based on the DNase I analysis, a -11.6-kb human HO-1 promoter construct was generated and elicited a 2.5-fold increase in reporter activity, indicating that 13-HPODE-mediated human HO-1 induction requires, at least in part, sequences that reside between 9.1 and 11.6 kb of the human HO-1 promoter.
assistant
Elucidation of the molecular mechanisms which control HO-1 gene expression will allow us to develop therapeutic strategies to enhance the cytoprotective potential of HO-1 in atherosclerosis. Final Decision: yes