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• W2129338565 endingPage "L697" @default.
• W2129338565 startingPage "L686" @default.
• W2129338565 abstract "Increased pulmonary endothelial cGMP was shown to prevent endothelial barrier dysfunction through activation of protein kinase G (PKG I ). Vasodilator-stimulated phosphoprotein (VASP) has been hypothesized to mediate PKG I barrier protection because VASP is a cytoskeletal phosphorylation target of PKG I expressed in cell-cell junctions. Unphosphorylated VASP was proposed to increase paracellular permeability through actin polymerization and stress fiber bundling, a process inhibited by PKG I -mediated phosphorylation of Ser 157 and Ser 239 . To test this hypothesis, we examined the role of VASP in the transient barrier dysfunction caused by H 2 O 2 in human pulmonary artery endothelial cell (HPAEC) monolayers studied without and with PKG I expression introduced by adenoviral infection (Ad.PKG). In the absence of PKG I expression, H 2 O 2 (100–250 μM) caused a transient increased permeability and pSer 157 -VASP formation that were both attenuated by protein kinase C inhibition. Potentiation of VASP Ser 157 phosphorylation by either phosphatase 2B inhibition with cyclosporin or protein kinase A activation with forskolin prolonged, rather than inhibited, the increased permeability caused by H 2 O 2 . With Ad.PKG infection, inhibition of VASP expression with small interfering RNA exacerbated H 2 O 2 -induced barrier dysfunction but had no effect on cGMP-mediated barrier protection. In addition, expression of a Ser-double phosphomimetic mutant VASP failed to reproduce the protective effects of activated PKG I . Finally, expression of a Ser-double phosphorylation-resistant VASP failed to interfere with the ability of cGMP/PKG I to attenuate H 2 O 2 -induced disruption of VE-cadherin homotypic binding. Our results suggest that VASP phosphorylation does not explain the protective effect of cGMP/PKG I on H 2 O 2 -induced endothelial barrier dysfunction in HPAEC." @default.
• W2129338565 created "2016-06-24" @default.
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• W2129338565 date "2008-04-01" @default.
• W2129338565 modified "2023-10-15" @default.
• W2129338565 title "Role of vasodilator-stimulated phosphoprotein in cGMP-mediated protection of human pulmonary artery endothelial barrier function" @default.
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• W2129338565 doi "https://doi.org/10.1152/ajplung.00417.2007" @default.
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