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H(2)O(2)-mediated permeability II: importance of tyrosine phosphatase and kinase activity.
- Source :
-
American journal of physiology. Cell physiology [Am J Physiol Cell Physiol] 2001 Dec; Vol. 281 (6), pp. C1940-7. - Publication Year :
- 2001
-
Abstract
- We previously reported that exposure of endothelial cells to H(2)O(2) results in a loss of cell-cell apposition and increased endothelial solute permeability. The purpose of this study was to determine how tyrosine phosphorylation and tyrosine phosphatases contribute to oxidant-mediated disorganization of endothelial cell junctions. We found that H(2)O(2) caused a rapid decrease in total cellular phosphatase activity that facilitates a compensatory increase in cellular phosphotyrosine residues. H(2)O(2) exposure also results in increased endothelial monolayer permeability, which was attenuated by pp60, an inhibitor of src kinase. Inhibition of protein tyrosine phosphatase activity by phenylarsine oxide (PAO) demonstrated a similar permeability profile compared with H(2)O(2), suggesting that tyrosine phosphatase activity is important in maintaining a normal endothelial solute barrier. Immunofluorescence shows that H(2)O(2) exposure caused a loss of pan-reactive cadherin and beta-catenin from cell junctions that was not blocked by the src kinase inhibitor PP1. H(2)O(2) also caused beta-catenin to dissociate from the endothelial cytoskeleton, which was not prevented by PP1. Finally, we determined that PP1 did not prevent cadherin internalization. These data suggest that oxidants like H(2)O(2) produce biological effects through protein phosphotyrosine modifications by decreasing total cellular phosphatase activity combined with increased src kinase activity, resulting in increased endothelial solute permeability.
- Subjects :
- Animals
Arsenicals pharmacology
Cadherins metabolism
Cattle
Cytoskeletal Proteins metabolism
Cytoskeleton metabolism
Endocytosis physiology
Endothelium, Vascular cytology
Enzyme Inhibitors pharmacology
Oxidants pharmacology
Phosphorylation
Protein Tyrosine Phosphatases antagonists & inhibitors
Pulmonary Artery anatomy & histology
beta Catenin
src-Family Kinases antagonists & inhibitors
Cell Membrane Permeability physiology
Endothelium, Vascular drug effects
Endothelium, Vascular enzymology
Hydrogen Peroxide pharmacology
Phosphotyrosine metabolism
Protein Tyrosine Phosphatases metabolism
Trans-Activators
src-Family Kinases metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0363-6143
- Volume :
- 281
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- American journal of physiology. Cell physiology
- Publication Type :
- Academic Journal
- Accession number :
- 11698252
- Full Text :
- https://doi.org/10.1152/ajpcell.2001.281.6.C1940