Heme Oxygenase-1 Protects Endothelial Cells from the Toxicity of Air Pollutant Chemicals
| Autor: | Aaron Lulla, Akeem O. Lawal, Michael Dittmar, Min Zhang, Jesus A. Araujo |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Time Factors
Cell Survival Toxicology Transfection complex mixtures Risk Assessment Article Proinflammatory cytokine Gene silencing Humans Viability assay Enzyme Inhibitors Cells Cultured Vehicle Emissions Pharmacology chemistry.chemical_classification Reactive oxygen species Air Pollutants Expression vector Dose-Response Relationship Drug L-Lactate Dehydrogenase Cell adhesion molecule Endothelial Cells respiratory system Cell biology respiratory tract diseases Heme oxygenase Oxidative Stress chemistry Biochemistry Toxicity Unfolded Protein Response Particulate Matter RNA Interference Inflammation Mediators Reactive Oxygen Species Cell Adhesion Molecules Heme Oxygenase-1 |
| Popis: | Diesel exhaust particles (DEPs) are a major component of diesel emissions, responsible for a large portion of their toxicity. In this study, we examined the toxic effects of DEPs on endothelial cells and the role of DEP-induced heme oxygenase-1 (HO-1) expression. Human microvascular endothelial cells (HMECs) were treated with an organic extract of DEPs from an automobile engine (A-DEP) or a forklift engine (F-DEP) for 1 and 4h. ROS generation, cell viability, lactate dehydrogenase leakage, expression of HO-1, inflammatory genes, cell adhesion molecules and unfolded protein respone (UPR) gene were assessed. HO-1 expression and/or activity were inhibited by siRNA or tin protoporphyrin (Sn PPIX) and enhanced by an expression plasmid or cobalt protoporphyrin (CoPPIX). Exposure to 25μg/ml of A-DEP and F-DEP significantly induced ROS production, cellular toxicity and greater levels of inflammatory and cellular adhesion molecules but to a different degree. Inhibition of HO-1 enzymatic activity with SnPPIX and silencing of the HO-1 gene by siRNA enhanced DEP-induced ROS production, further decreased cell viability and increased expression of inflammatory and cell adhesion molecules. On the other hand, overexpression of the HO-1 gene by a pcDNA 3.1D/V5-HO-1 plasmid significantly mitigated ROS production, increased cell survival and decreased the expression of inflammatory genes. HO-1 expression protected HMECs from DEP-induced prooxidative and proinflammatory effects. Modulation of HO-1 expression could potentially serve as a therapeutic target in an attempt to inhibit the cardiovascular effects of ambient PM. |
| Databáze: | OpenAIRE |
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