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Role of truncated oxidized phospholipids in acute endothelial barrier dysfunction caused by particulate matter

Particulate matter (PM) air pollution is a global environmental health problem contributing to more severe lung inflammation and injury. However, the molecular and cellular mechanisms of PM-induced exacerbation of lung barrier dysfunction and injury are not well understood. In the current study, we...

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Autores principales: Karki, Pratap, Meliton, Angelo, Shah, Alok, Tian, Yufeng, Ohmura, Tomomi, Sarich, Nicolene, Birukova, Anna A., Birukov, Konstantin G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6231611/
https://www.ncbi.nlm.nih.gov/pubmed/30419037
http://dx.doi.org/10.1371/journal.pone.0206251
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author Karki, Pratap
Meliton, Angelo
Shah, Alok
Tian, Yufeng
Ohmura, Tomomi
Sarich, Nicolene
Birukova, Anna A.
Birukov, Konstantin G.
author_facet Karki, Pratap
Meliton, Angelo
Shah, Alok
Tian, Yufeng
Ohmura, Tomomi
Sarich, Nicolene
Birukova, Anna A.
Birukov, Konstantin G.
author_sort Karki, Pratap
collection PubMed
description Particulate matter (PM) air pollution is a global environmental health problem contributing to more severe lung inflammation and injury. However, the molecular and cellular mechanisms of PM-induced exacerbation of lung barrier dysfunction and injury are not well understood. In the current study, we tested a hypothesis that PM exacerbates vascular barrier dysfunction via ROS-induced generation of truncated oxidized phospholipids (Tr-OxPLs). Treatment of human pulmonary endothelial cells with PM caused endothelial cell barrier disruption in a dose-dependent fashion. Biochemical analysis showed destabilization of cell junctions by PM via tyrosine phosphorylation and internalization of VE-cadherin. These events were accompanied by PM-induced generation of Tr-OxPLs, detected by mass spectrometry analysis. Furthermore, purified Tr-OxPLs: POVPC, PGPC and lyso-PC alone, caused a rapid increase in endothelial permeability and augmented pulmonary endothelial barrier dysfunction induced by submaximal doses of PM. In support of a role of TR-OxPLs-dependent mechanism in mediation of PM effects, ectopic expression of intracellular type 2 platelet-activating factor acetylhydrolase (PAFAH2), which specifically hydrolyzes Tr-OxPLs, significantly attenuated PM-induced endothelial hyperpermeability. In summary, this study uncovered a novel mechanism of PM-induced sustained dysfunction of pulmonary endothelial cell barrier which is driven by PM-induced generation of truncated products of phospholipid oxidation causing destabilization of cell junctions.
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spelling pubmed-62316112018-11-19 Role of truncated oxidized phospholipids in acute endothelial barrier dysfunction caused by particulate matter Karki, Pratap Meliton, Angelo Shah, Alok Tian, Yufeng Ohmura, Tomomi Sarich, Nicolene Birukova, Anna A. Birukov, Konstantin G. PLoS One Research Article Particulate matter (PM) air pollution is a global environmental health problem contributing to more severe lung inflammation and injury. However, the molecular and cellular mechanisms of PM-induced exacerbation of lung barrier dysfunction and injury are not well understood. In the current study, we tested a hypothesis that PM exacerbates vascular barrier dysfunction via ROS-induced generation of truncated oxidized phospholipids (Tr-OxPLs). Treatment of human pulmonary endothelial cells with PM caused endothelial cell barrier disruption in a dose-dependent fashion. Biochemical analysis showed destabilization of cell junctions by PM via tyrosine phosphorylation and internalization of VE-cadherin. These events were accompanied by PM-induced generation of Tr-OxPLs, detected by mass spectrometry analysis. Furthermore, purified Tr-OxPLs: POVPC, PGPC and lyso-PC alone, caused a rapid increase in endothelial permeability and augmented pulmonary endothelial barrier dysfunction induced by submaximal doses of PM. In support of a role of TR-OxPLs-dependent mechanism in mediation of PM effects, ectopic expression of intracellular type 2 platelet-activating factor acetylhydrolase (PAFAH2), which specifically hydrolyzes Tr-OxPLs, significantly attenuated PM-induced endothelial hyperpermeability. In summary, this study uncovered a novel mechanism of PM-induced sustained dysfunction of pulmonary endothelial cell barrier which is driven by PM-induced generation of truncated products of phospholipid oxidation causing destabilization of cell junctions. Public Library of Science 2018-11-12 /pmc/articles/PMC6231611/ /pubmed/30419037 http://dx.doi.org/10.1371/journal.pone.0206251 Text en © 2018 Karki et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Karki, Pratap
Meliton, Angelo
Shah, Alok
Tian, Yufeng
Ohmura, Tomomi
Sarich, Nicolene
Birukova, Anna A.
Birukov, Konstantin G.
Role of truncated oxidized phospholipids in acute endothelial barrier dysfunction caused by particulate matter
title Role of truncated oxidized phospholipids in acute endothelial barrier dysfunction caused by particulate matter
title_full Role of truncated oxidized phospholipids in acute endothelial barrier dysfunction caused by particulate matter
title_fullStr Role of truncated oxidized phospholipids in acute endothelial barrier dysfunction caused by particulate matter
title_full_unstemmed Role of truncated oxidized phospholipids in acute endothelial barrier dysfunction caused by particulate matter
title_short Role of truncated oxidized phospholipids in acute endothelial barrier dysfunction caused by particulate matter
title_sort role of truncated oxidized phospholipids in acute endothelial barrier dysfunction caused by particulate matter
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6231611/
https://www.ncbi.nlm.nih.gov/pubmed/30419037
http://dx.doi.org/10.1371/journal.pone.0206251
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