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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...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2018
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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. |
format | Online Article Text |
id | pubmed-6231611 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
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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