| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Department of Medicine, Division of Pulmonary and Critical Care Medicine, The Johns Hopkins Medical Institutions, Baltimore, MD, USA
2 Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, MD, USA
* To whom correspondence should be addressed. E-mail: dpearse{at}jhmi.edu.
Increases in endothelial cyclic guanosine 3',5'- monophosphate (cGMP) prevent oxidantmediated
endothelial barrier dysfunction but the downstream mechanisms remain unclear.
To determine the role of cGMP-dependent protein kinase (PKGI), human pulmonary artery
endothelial cells (HPAEC) lacking PKGI expression were infected with a recombinant
adenovirus encoding PKGI
(Ad.PKG) and compared to uninfected and control-infected
(Ad.gal) HPAECs. Transendothelial electrical resistance, an index of permeability, was
measured after H2O2 (250 µM) exposure with or without pretreatment with 8pCPT-cGMP.
HPAEC infected with Ad.PKG, but not Ad.gal, expressed PKGI protein and demonstrated
ser239 and ser157 phosphorylation of vasodilator-stimulated phosphoprotein following
treatment with 8pCPT-cGMP. Adenoviral infection decreased basal permeability equally in
Ad.PKG and Ad.gal-infected HPAEC compared to uninfected cells. Treatment with
8pCPT-cGMP (100 µM) caused a PKGI-independent decrease in permeability (8.2 ± 0.6%).
In all three groups, H2O2 (250 µM) caused a similar ~35% increase in permeability
associated with increased actin stress fiber formation, intercellular gaps, loss of membrane
VE-cadherin, and increased intracellular calcium concentration ([Ca2+]i). In uninfected and
Ad.gal-infected HPAECs, pretreatment with 8pCPT-cGMP (100 µM) partially blocked the
increased permeability induced by H2O2. In Ad.PKG-infected HPAECs, 8pCPT-cGMP (50
µM) prevented the H2O2-induced TER decrease, cytoskeletal rearrangement, and loss of
junctional VE-cadherin. 8pCPT-cGMP attenuated the peak [Ca2+]i caused by H2O2 similarly
(23%) in Ad.gal and Ad.PKG-infected HPAEC indicating a PKGI-independent effect.
These data suggest that cGMP decreased HPAEC basal permeability by a PKGI independent process whereas the ability of cGMP to prevent H2O2-induced barrier
dysfunction was predominantly mediated by PKGI through a Ca2+-independent mechanism.
This article has been cited by other articles:
|
|
 |
|
  E. P. Schmidt, M. Damarla, O. Rentsendorj, L. E. Servinsky, B. Zhu, A. Moldobaeva, A. Gonzalez, P. M. Hassoun, and D. B. Pearse Soluble guanylyl cyclase contributes to ventilator-induced lung injury in mice Am J Physiol Lung Cell Mol Physiol, December 1, 2008; 295(6): L1056 - L1065. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Dodd-o, M. L. Hristopoulos, K. Kibler, J. Gutkowska, S. Mukaddam-Daher, A. Gonzalez, L. E. Welsh-Servinsky, and D. B. Pearse The role of natriuretic peptide receptor-A signaling in unilateral lung ischemia-reperfusion injury in the intact mouse Am J Physiol Lung Cell Mol Physiol, April 1, 2008; 294(4): L714 - L723. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Rentsendorj, T. Mirzapoiazova, D. Adyshev, L. E. Servinsky, T. Renne, A. D. Verin, and D. B. Pearse Role of vasodilator-stimulated phosphoprotein in cGMP-mediated protection of human pulmonary artery endothelial barrier function Am J Physiol Lung Cell Mol Physiol, April 1, 2008; 294(4): L686 - L697. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W.-L. Yeh, D.-Y. Lu, C.-J. Lin, H.-C. Liou, and W.-M. Fu Inhibition of Hypoxia-Induced Increase of Blood-Brain Barrier Permeability by YC-1 through the Antagonism of HIF-1{alpha} Accumulation and VEGF Expression Mol. Pharmacol., August 1, 2007; 72(2): 440 - 449. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Boerrigter, L. C. Costello-Boerrigter, A. Cataliotti, H. Lapp, J.-P. Stasch, and J. C. Burnett Jr Targeting Heme-Oxidized Soluble Guanylate Cyclase in Experimental Heart Failure Hypertension, May 1, 2007; 49(5): 1128 - 1133. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Glynos, A. Kotanidou, S. E. Orfanos, Z. Zhou, D. C. M. Simoes, C. Magkou, C. Roussos, and A. Papapetropoulos Soluble guanylyl cyclase expression is reduced in LPS-induced lung injury Am J Physiol Regulatory Integrative Comp Physiol, April 1, 2007; 292(4): R1448 - R1455. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. W. Orr, R. Stockton, M. B. Simmers, J. M. Sanders, I. J. Sarembock, B. R. Blackman, and M. A. Schwartz Matrix-specific p21-activated kinase activation regulates vascular permeability in atherogenesis J. Cell Biol., February 26, 2007; 176(5): 719 - 727. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
