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Title: Heme oxygenase-1 protects endothelial cells from the toxicity of air pollutant chemicals

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 expressionmore » 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.« less

Authors:
; ;  [1];  [1]
  1. Division of Cardiology, David Geffen School of Medicine, University of California, Los Angeles, 10833 Le Conte Avenue, CHS 43-264, Los Angeles, CA 90095 (United States)
Publication Date:
OSTI Identifier:
22465745
Resource Type:
Journal Article
Journal Name:
Toxicology and Applied Pharmacology
Additional Journal Information:
Journal Volume: 284; Journal Issue: 3; Other Information: Copyright (c) 2015 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0041-008X
Country of Publication:
United States
Language:
English
Subject:
60 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

Citation Formats

Lawal, Akeem O., Zhang, Min, Dittmar, Michael, Lulla, Aaron, Molecular Toxicology Interdepartmental Program, University of California, Los Angeles, Araujo, Jesus A., E-mail: JAraujo@mednet.ucla.edu, Molecular Toxicology Interdepartmental Program, University of California, Los Angeles, and Molecular Biology Institute, University of California, Los Angeles. Heme oxygenase-1 protects endothelial cells from the toxicity of air pollutant chemicals. United States: N. p., 2015. Web. doi:10.1016/J.TAAP.2015.01.010.
Lawal, Akeem O., Zhang, Min, Dittmar, Michael, Lulla, Aaron, Molecular Toxicology Interdepartmental Program, University of California, Los Angeles, Araujo, Jesus A., E-mail: JAraujo@mednet.ucla.edu, Molecular Toxicology Interdepartmental Program, University of California, Los Angeles, & Molecular Biology Institute, University of California, Los Angeles. Heme oxygenase-1 protects endothelial cells from the toxicity of air pollutant chemicals. United States. https://doi.org/10.1016/J.TAAP.2015.01.010
Lawal, Akeem O., Zhang, Min, Dittmar, Michael, Lulla, Aaron, Molecular Toxicology Interdepartmental Program, University of California, Los Angeles, Araujo, Jesus A., E-mail: JAraujo@mednet.ucla.edu, Molecular Toxicology Interdepartmental Program, University of California, Los Angeles, and Molecular Biology Institute, University of California, Los Angeles. 2015. "Heme oxygenase-1 protects endothelial cells from the toxicity of air pollutant chemicals". United States. https://doi.org/10.1016/J.TAAP.2015.01.010.
@article{osti_22465745,
title = {Heme oxygenase-1 protects endothelial cells from the toxicity of air pollutant chemicals},
author = {Lawal, Akeem O. and Zhang, Min and Dittmar, Michael and Lulla, Aaron and Molecular Toxicology Interdepartmental Program, University of California, Los Angeles and Araujo, Jesus A., E-mail: JAraujo@mednet.ucla.edu and Molecular Toxicology Interdepartmental Program, University of California, Los Angeles and Molecular Biology Institute, University of California, Los Angeles},
abstractNote = {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.},
doi = {10.1016/J.TAAP.2015.01.010},
url = {https://www.osti.gov/biblio/22465745}, journal = {Toxicology and Applied Pharmacology},
issn = {0041-008X},
number = 3,
volume = 284,
place = {United States},
year = {Fri May 01 00:00:00 EDT 2015},
month = {Fri May 01 00:00:00 EDT 2015}
}