scholarly journals Peroxynitrite-dependent activation of protein phosphatase type 2A mediates microvascular endothelial barrier dysfunction

2008 ◽  
Vol 81 (1) ◽  
pp. 38-45 ◽  
Author(s):  
F. Wu ◽  
J. X. Wilson
Keyword(s):  
Protein Phosphatase ◽  
Endothelial Barrier ◽  
Barrier Dysfunction ◽  
Endothelial Barrier Dysfunction ◽  
Microvascular Endothelial ◽  
Protein Phosphatase Type

scholarly journals The HSP90 Inhibitor, AUY-922, Protects and Repairs Human Lung Microvascular Endothelial Cells from Hydrochloric Acid-Induced Endothelial Barrier Dysfunction

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1489
Author(s):  
Ruben M. L. Colunga Biancatelli ◽  
Pavel Solopov ◽  
Betsy Gregory ◽  
John D. Catravas
Keyword(s):  
Endothelial Cells ◽  
Hydrochloric Acid ◽  
Human Lung ◽  
Hsp90 Inhibitor ◽  
Endothelial Barrier ◽  
Microvascular Endothelial Cells ◽  
Dependent Manner ◽  
Barrier Dysfunction ◽  
Endothelial Barrier Dysfunction ◽  
Microvascular Endothelial

Exposure to hydrochloric acid (HCl) leads acutely to asthma-like symptoms, acute respiratory distress syndrome (ARDS), including compromised alveolo-capillary barrier, and respiratory failure. To better understand the direct effects of HCl on pulmonary endothelial function, we studied the characteristics of HCl-induced endothelial barrier dysfunction in primary cultures of human lung microvascular endothelial cells (HLMVEC), defined the involved molecular pathways, and tested the potentially beneficial effects of Heat Shock Protein 90 (HSP90) inhibitors. HCl impaired barrier function in a time- and concentration-dependent manner and was associated with activation of Protein Kinase B (AKT), Ras homolog family member A (RhoA) and myosin light chain 2 (MLC2), as well as loss of plasmalemmal VE-cadherin, rearrangement of cortical actin, and appearance of inter-endothelial gaps. Pre-treatment or post-treatment of HLMVEC with AUY-922, a third-generation HSP90 inhibitor, prevented and restored HCl-induced endothelial barrier dysfunction. AUY-922 increased the expression of HSP70 and inhibited the activation (phosphorylation) of extracellular-signal regulated kinase (ERK) and AKT. AUY-922 also prevented the HCl-induced activation of RhoA and MLC2 and the internalization of plasmalemmal VE-cadherin. We conclude that, by increasing the expression of cytoprotective proteins, interfering with actomyosin contractility, and enhancing the expression of junction proteins, inhibition of HSP90 may represent a useful approach for the management of HCl-induced endothelial dysfunction and acute lung injury.

Effect of cGMP on Lung Microvascular Endothelial Barrier Dysfunction Following Hydrogen Peroxide

Endothelium ◽  
2003 ◽  
Vol 10 (6) ◽  
pp. 309-317 ◽  
Author(s):  
David B. Pearse ◽  
Larissa A. Shimoda ◽  
Alexander D. Verin ◽  
Natalia Bogatcheva ◽  
Cheil Moon ◽  
...  
Keyword(s):  
Hydrogen Peroxide ◽  
Endothelial Barrier ◽  
Barrier Dysfunction ◽  
Endothelial Barrier Dysfunction ◽  
Microvascular Endothelial

Effect of cGMP on Lung Microvascular Endothelial Barrier Dysfunction Following Hydrogen Peroxide

Endothelium ◽  
2003 ◽  
Vol 10 (6) ◽  
pp. 309-317 ◽  
Author(s):  
David Pearse ◽  
Larissa Shimoda ◽  
Alexander Verin ◽  
Natalia Bogatcheva ◽  
Cheil Moon ◽  
...  
Keyword(s):  
Hydrogen Peroxide ◽  
Endothelial Barrier ◽  
Barrier Dysfunction ◽  
Endothelial Barrier Dysfunction ◽  
Microvascular Endothelial
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