Get 20M+ Full-Text Papers For Less Than $1.50/day. Start a 7-Day Trial for You or Your Team.

Learn More →

Oxidized phospholipids mediate occludin expression and phosphorylation in vascular endothelial cells

Oxidized phospholipids mediate occludin expression and phosphorylation in vascular endothelial cells Oxidized L -α-1-palmitoyl-2-arachidonoyl- sn -glycero-3-phosphorylcholine (OxPAPC), a component of minimally modified LDL, induces production of proinflammatory cytokines and development of atherosclerotic lesions. We tested the hypothesis that OxPAPC alters expression, phosphorylation, and localization of tight junction (TJ) proteins, particularly occludin, a transmembrane TJ protein. OxPAPC reduced total occludin protein and increased occludin phosphorylation dose dependently (10–50 µg/ml) and time dependently in bovine aortic endothelial cells. OxPAPC decreased occludin mRNA and reduced the immunoreactivity of zonula occludens-1 at the cell-cell contacts. Furthermore, OxPAPC increased the diffusive flux of 10-kDa dextran in a dose-dependent manner. O 2 – · production by bovine aortic endothelial cells increased nearly twofold after exposure to OxPAPC. Also, enzymatic generation of O 2 – · by xanthine oxidase-lumazine and H 2 O 2 by glucose oxidase-glucose increased occludin phosphorylation, implicating reactive oxygen species as modulators of the OxPAPC effects on occludin phosphorylation. Superoxide dismutase and/or catalase blocked the effects of OxPAPC on occludin protein content and phosphorylation, occludin mRNA, zonula occludens-1 immunoreactivity, and diffusive flux of 10-kDa dextran. These findings suggest that changes in TJ proteins are potential mechanisms by which OxPAPC compromises the barrier properties of the vascular endothelium. OxPAPC-induced disruption of TJs, which likely facilitates transmigration of LDL and inflammatory cells into the subendothelial layers, may be mediated by reactive oxygen species. oxidized L -α-1-palmitoyl-2-arachidonoyl- sn -glycero-3-phosphorylcholine; reactive oxygen species Address for reprint requests and other correspondence: L. DeMaio, Dept. of Biomedical Engineering and Division of Cardiovascular Medicine, DRB 398, USC, Los Angeles, CA 90089 (e-mail: [email protected] ) http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png AJP - Heart and Circulatory Physiology The American Physiological Society

Oxidized phospholipids mediate occludin expression and phosphorylation in vascular endothelial cells

Download PDF
11 pages

Loading next page...
 
/lp/the-american-physiological-society/oxidized-phospholipids-mediate-occludin-expression-and-phosphorylation-Tt54VlyINU

References (66)

Publisher
The American Physiological Society
Copyright
Copyright © 2011 the American Physiological Society
ISSN
0363-6135
eISSN
1522-1539
DOI
10.1152/ajpheart.00554.2005
pmid
16172163
Publisher site
See Article on Publisher Site

Abstract

Oxidized L -α-1-palmitoyl-2-arachidonoyl- sn -glycero-3-phosphorylcholine (OxPAPC), a component of minimally modified LDL, induces production of proinflammatory cytokines and development of atherosclerotic lesions. We tested the hypothesis that OxPAPC alters expression, phosphorylation, and localization of tight junction (TJ) proteins, particularly occludin, a transmembrane TJ protein. OxPAPC reduced total occludin protein and increased occludin phosphorylation dose dependently (10–50 µg/ml) and time dependently in bovine aortic endothelial cells. OxPAPC decreased occludin mRNA and reduced the immunoreactivity of zonula occludens-1 at the cell-cell contacts. Furthermore, OxPAPC increased the diffusive flux of 10-kDa dextran in a dose-dependent manner. O 2 – · production by bovine aortic endothelial cells increased nearly twofold after exposure to OxPAPC. Also, enzymatic generation of O 2 – · by xanthine oxidase-lumazine and H 2 O 2 by glucose oxidase-glucose increased occludin phosphorylation, implicating reactive oxygen species as modulators of the OxPAPC effects on occludin phosphorylation. Superoxide dismutase and/or catalase blocked the effects of OxPAPC on occludin protein content and phosphorylation, occludin mRNA, zonula occludens-1 immunoreactivity, and diffusive flux of 10-kDa dextran. These findings suggest that changes in TJ proteins are potential mechanisms by which OxPAPC compromises the barrier properties of the vascular endothelium. OxPAPC-induced disruption of TJs, which likely facilitates transmigration of LDL and inflammatory cells into the subendothelial layers, may be mediated by reactive oxygen species. oxidized L -α-1-palmitoyl-2-arachidonoyl- sn -glycero-3-phosphorylcholine; reactive oxygen species Address for reprint requests and other correspondence: L. DeMaio, Dept. of Biomedical Engineering and Division of Cardiovascular Medicine, DRB 398, USC, Los Angeles, CA 90089 (e-mail: [email protected] )

Journal

AJP - Heart and Circulatory Physiology – The American Physiological Society

Published: Feb 1, 2006

There are no references for this article.