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Author Lawal, Akeem O. ♦ Zhang, Min ♦ Dittmar, Michael ♦ Lulla, Aaron ♦ Araujo, Jesus A.
Source United States Department of Energy Office of Scientific and Technical Information
Content type Text
Language English
Subject Keyword APPLIED LIFE SCIENCES ♦ ADHESION ♦ AIR POLLUTION ♦ CARDIOVASCULAR DISEASES ♦ FLUORESCENCE ♦ GENES ♦ HEME ♦ INFLAMMATION ♦ INHIBITION ♦ LACTATE DEHYDROGENASE ♦ MOLECULES ♦ ORGANIC MATTER ♦ OXYGEN ♦ STRESSES ♦ TIN ♦ TOXICITY ♦ TRANSCRIPTION FACTORS ♦ VIABILITY
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 4 h. 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 25 μg/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. - Highlights: • We examined the role of HO-1 expression on diesel exhaust particle (DEP) in endothelial cells. • DEPs exert cytotoxic and inflammatory effects on human microvascular endothelial cells (HMECs). • DEPs induce HO-1 expression in HMECs. • HO-1 protects against the oxidative stress induced by DEps. • HO-1 attenuates the proinflammatory effects induced by DEPs.
ISSN 0041008X
Educational Use Research
Learning Resource Type Article
Publisher Date 2015-05-01
Publisher Place United States
Journal Toxicology and Applied Pharmacology
Volume Number 284
Issue Number 3


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