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GRP78 is a novel receptor initiating a vascular barrier protective response to oxidized phospholipids
Vascular integrity and the maintenance of blood vessel continuity are fundamental features of the circulatory system maintained through endothelial cell–cell junctions. Defects in the endothelial barrier become an initiating factor in several pathologies, including ischemia/reperfusion, tumor angiog...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4072574/ https://www.ncbi.nlm.nih.gov/pubmed/24829380 http://dx.doi.org/10.1091/mbc.E13-12-0743 |
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author | Birukova, Anna A. Singleton, Patrick A. Gawlak, Grzegorz Tian, Xinyong Mirzapoiazova, Tamara Mambetsariev, Bolot Dubrovskyi, Oleksii Oskolkova, Olga V. Bochkov, Valery N. Birukov, Konstantin G. |
author_facet | Birukova, Anna A. Singleton, Patrick A. Gawlak, Grzegorz Tian, Xinyong Mirzapoiazova, Tamara Mambetsariev, Bolot Dubrovskyi, Oleksii Oskolkova, Olga V. Bochkov, Valery N. Birukov, Konstantin G. |
author_sort | Birukova, Anna A. |
collection | PubMed |
description | Vascular integrity and the maintenance of blood vessel continuity are fundamental features of the circulatory system maintained through endothelial cell–cell junctions. Defects in the endothelial barrier become an initiating factor in several pathologies, including ischemia/reperfusion, tumor angiogenesis, pulmonary edema, sepsis, and acute lung injury. Better understanding of mechanisms stimulating endothelial barrier enhancement may provide novel therapeutic strategies. We previously reported that oxidized phospholipids (oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine [OxPAPC]) promote endothelial cell (EC) barrier enhancement both in vitro and in vivo. This study examines the initiating mechanistic events triggered by OxPAPC to increase vascular integrity. Our data demonstrate that OxPAPC directly binds the cell membrane–localized chaperone protein, GRP78, associated with its cofactor, HTJ-1. OxPAPC binding to plasma membrane–localized GRP78 leads to GRP78 trafficking to caveolin-enriched microdomains (CEMs) on the cell surface and consequent activation of sphingosine 1-phosphate receptor 1, Src and Fyn tyrosine kinases, and Rac1 GTPase, processes essential for cytoskeletal reorganization and EC barrier enhancement. Using animal models of acute lung injury with vascular hyperpermeability, we observed that HTJ-1 knockdown blocked OxPAPC protection from interleukin-6 and ventilator-induced lung injury. Our data indicate for the first time an essential role of GRP78 and HTJ-1 in OxPAPC-mediated CEM dynamics and enhancement of vascular integrity. |
format | Online Article Text |
id | pubmed-4072574 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-40725742014-09-16 GRP78 is a novel receptor initiating a vascular barrier protective response to oxidized phospholipids Birukova, Anna A. Singleton, Patrick A. Gawlak, Grzegorz Tian, Xinyong Mirzapoiazova, Tamara Mambetsariev, Bolot Dubrovskyi, Oleksii Oskolkova, Olga V. Bochkov, Valery N. Birukov, Konstantin G. Mol Biol Cell Articles Vascular integrity and the maintenance of blood vessel continuity are fundamental features of the circulatory system maintained through endothelial cell–cell junctions. Defects in the endothelial barrier become an initiating factor in several pathologies, including ischemia/reperfusion, tumor angiogenesis, pulmonary edema, sepsis, and acute lung injury. Better understanding of mechanisms stimulating endothelial barrier enhancement may provide novel therapeutic strategies. We previously reported that oxidized phospholipids (oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine [OxPAPC]) promote endothelial cell (EC) barrier enhancement both in vitro and in vivo. This study examines the initiating mechanistic events triggered by OxPAPC to increase vascular integrity. Our data demonstrate that OxPAPC directly binds the cell membrane–localized chaperone protein, GRP78, associated with its cofactor, HTJ-1. OxPAPC binding to plasma membrane–localized GRP78 leads to GRP78 trafficking to caveolin-enriched microdomains (CEMs) on the cell surface and consequent activation of sphingosine 1-phosphate receptor 1, Src and Fyn tyrosine kinases, and Rac1 GTPase, processes essential for cytoskeletal reorganization and EC barrier enhancement. Using animal models of acute lung injury with vascular hyperpermeability, we observed that HTJ-1 knockdown blocked OxPAPC protection from interleukin-6 and ventilator-induced lung injury. Our data indicate for the first time an essential role of GRP78 and HTJ-1 in OxPAPC-mediated CEM dynamics and enhancement of vascular integrity. The American Society for Cell Biology 2014-07-01 /pmc/articles/PMC4072574/ /pubmed/24829380 http://dx.doi.org/10.1091/mbc.E13-12-0743 Text en © 2014 Birukova, Singleton, et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society of Cell Biology. |
spellingShingle | Articles Birukova, Anna A. Singleton, Patrick A. Gawlak, Grzegorz Tian, Xinyong Mirzapoiazova, Tamara Mambetsariev, Bolot Dubrovskyi, Oleksii Oskolkova, Olga V. Bochkov, Valery N. Birukov, Konstantin G. GRP78 is a novel receptor initiating a vascular barrier protective response to oxidized phospholipids |
title | GRP78 is a novel receptor initiating a vascular barrier protective response to oxidized phospholipids |
title_full | GRP78 is a novel receptor initiating a vascular barrier protective response to oxidized phospholipids |
title_fullStr | GRP78 is a novel receptor initiating a vascular barrier protective response to oxidized phospholipids |
title_full_unstemmed | GRP78 is a novel receptor initiating a vascular barrier protective response to oxidized phospholipids |
title_short | GRP78 is a novel receptor initiating a vascular barrier protective response to oxidized phospholipids |
title_sort | grp78 is a novel receptor initiating a vascular barrier protective response to oxidized phospholipids |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4072574/ https://www.ncbi.nlm.nih.gov/pubmed/24829380 http://dx.doi.org/10.1091/mbc.E13-12-0743 |
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