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Oxidized phospholipids mediate occludin expression and phosphorylation in vascular endothelial cells
- Source :
- American Journal of Physiology-Heart and Circulatory Physiology. 290:H674-H683
- Publication Year :
- 2006
- Publisher :
- American Physiological Society, 2006.
-
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. O2−· production by bovine aortic endothelial cells increased nearly twofold after exposure to OxPAPC. Also, enzymatic generation of O2−· by xanthine oxidase-lumazine and H2O2by 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.
- Subjects :
- Reactive oxygen species metabolism
Physiology
Gene Expression
Biology
Occludin
Permeability
Proinflammatory cytokine
Physiology (medical)
Animals
Phosphorylation
Aorta
Cells, Cultured
Modified ldl
chemistry.chemical_classification
Reactive oxygen species
Superoxide Dismutase
Extramural
Endothelial Cells
Membrane Proteins
Dextrans
Catalase
Phosphoproteins
Immunohistochemistry
Cell biology
chemistry
Phosphatidylcholines
Zonula Occludens-1 Protein
Cattle
Reactive Oxygen Species
Cardiology and Cardiovascular Medicine
Subjects
Details
- ISSN :
- 15221539 and 03636135
- Volume :
- 290
- Database :
- OpenAIRE
- Journal :
- American Journal of Physiology-Heart and Circulatory Physiology
- Accession number :
- edsair.doi.dedup.....c48fdcd28dea26b297b919a90ed9164a