Pulmonary endothelial cell signaling and function.
Trans Am Clin Climatol Assoc
; 119: 155-67; discussion 167-9, 2008.
Article
em En
| MEDLINE
| ID: mdl-18596849
ABSTRACT
RhoA is an important modulator of endothelial monolayer permeability. Posttranslational carboxyl methylation of small GTPases, such as RhoA and Ras, regulates subcellular localization and GTPase activity, resulting in altered cellular function. In this study, we investigated the role of RhoA carboxyl methylation in modulating endothelial monolayer permeability. We found that inhibition of isoprenylcysteine-O-carboxyl methyltransferase (ICMT) with adenosine plus homocysteine (Ado/HC) or N-acetyl-S-geranylgeranyl-L-cysteine (AGGC) decreased RhoA carboxyl methylation and activation, which correlated with decreased monolayer permeability of bovine pulmonary artery endothelial cells (BPAEC). Conversely, BPAEC stably overexpressing ICMT had enhanced endothelial monolayer permeability, associated with elevated RhoA carboxyl methylation and activation. These results suggest that ICMT modulates endothelial monolayer permeability by altering RhoA carboxyl methylation and activation. In addition, we demonstrated that adenosine deaminase inhibitor not only attenuated, but also rescued, lung edema induced by a non-inflammatory edemagenic agent. Our data suggest that increasing intracellular adenosine is a useful therapeutic strategy against diseases characterized by increased vascular permeability.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Artéria Pulmonar
/
Células Endoteliais
Limite:
Animals
Idioma:
En
Revista:
Trans Am Clin Climatol Assoc
Ano de publicação:
2008
Tipo de documento:
Article
País de afiliação:
Estados Unidos