Title: Heme oxygenase-1 protects endothelial cells from the toxicity of air pollutant chemicals.
Authors: Lawal, Akeem; Zhang, Min; Dittmar, Michael; Lulla, Aaron; Araujo, Jesus A
Published In Toxicol Appl Pharmacol, (2015 May 01)
Abstract: 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.
PubMed ID: 25620054
MeSH Terms: Air Pollutants/toxicity*; Cell Adhesion Molecules/metabolism; Cell Survival/drug effects; Cells, Cultured; Dose-Response Relationship, Drug; Endothelial Cells/drug effects*; Endothelial Cells/enzymology; Endothelial Cells/pathology; Enzyme Inhibitors/toxicity; Heme Oxygenase-1/antagonists & inhibitors; Heme Oxygenase-1/genetics; Heme Oxygenase-1/metabolism*; Humans; Inflammation Mediators/metabolism; L-Lactate Dehydrogenase/metabolism; Oxidative Stress/drug effects; Particulate Matter/toxicity*; RNA Interference; Reactive Oxygen Species/metabolism; Risk Assessment; Time Factors; Transfection; Unfolded Protein Response/drug effects; Vehicle Emissions/toxicity*