Key result
In human pulmonary artery endothelial cells, cGMP prevented H2O2-induced barrier dysfunction predominantly through a PKG(I)-mediated, Ca(2+)-independent mechanism.
Answers are grounded in this paper and cite their sources.
The ability of cGMP to prevent oxidant-induced barrier dysfunction in human pulmonary artery endothelial cells is predominantly mediated by PKG(I) through a Ca2+-independent mechanism.
Increases in endothelial cGMP prevent oxidant-mediated endothelial barrier dysfunction, but the downstream mechanisms remain unclear. To determine the role of cGMP-dependent protein kinase (PKG)(I), human pulmonary artery endothelial cells (HPAEC) lacking PKG(I) expression were infected with a recombinant adenovirus encoding PKG(Ibeta) (Ad.PKG) and compared with uninfected and control-infected (Ad.betagal) HPAEC. Transendothelial electrical resistance (TER), an index of permeability, was measured after H(2)O(2) (250 microM) exposure with or without pretreatment with 8-(4-chlorophenylthio)guanosine 3',5'-cyclic monophosphate (CPT-cGMP). HPAEC infected with Ad.PKG, but not Ad.betagal, expressed PKG(I) protein and demonstrated Ser(239) and Ser(157) phosphorylation of vasodilator-stimulated phosphoprotein after treatment with CPT-cGMP. Adenoviral infection decreased basal permeability equally in Ad.PKG- and Ad.betagal-infected HPAEC compared with uninfected cells. Treatment with CPT-cGMP (100 microM) caused a PKG(I)-independent decrease in permeability (8.2 +/- 0.6%). In all three groups, H(2)O(2) (250 microM) caused a similar approximately 35% increase in permeability associated with increased actin stress fiber formation, intercellular gaps, loss of membrane VE-cadherin, and increased intracellular Ca(2+) concentration ([Ca(2+)](i)). In uninfected and Ad.betagal-infected HPAEC, pretreatment with CPT-cGMP (100 microM) partially blocked the increased permeability induced by H(2)O(2). In Ad.PKG-infected HPAEC, CPT-cGMP (50 microM) prevented the H(2)O(2)-induced TER decrease, cytoskeletal rearrangement, and loss of junctional VE-cadherin. CPT-cGMP attenuated the peak [Ca(2+)](i) caused by H(2)O(2) similarly (23%) in Ad.betagal- and Ad.PKG-infected HPAEC, indicating a PKG(I)-independent effect. These data suggest that cGMP decreased HPAEC basal permeability by a PKG(I)-independent process, whereas the ability of cGMP to prevent H(2)O(2)-induced barrier dysfunction was predominantly mediated by PKG(I) through a Ca(2+)-independent mechanism.
No takes yet. Share an insight, caveat, or question.
Moldobaeva et al. (2005) studied Oxidant-mediated endothelial barrier dysfunction. Recombinant adenovirus encoding PKG(Ibeta) (Ad.PKG) and CPT-cGMP vs. Uninfected and control-infected (Ad.betagal) HPAEC was evaluated on Transendothelial electrical resistance (TER) / permeability after H2O2 exposure. In human pulmonary artery endothelial cells, cGMP prevented H2O2-induced barrier dysfunction predominantly through a PKG(I)-mediated, Ca(2+)-independent mechanism.
Synapse has enriched 10 related papers. Consider them for comparative context: