Glucosylation of small GTP-binding Rho proteins disrupts endothelial barrier function
| Autor: | S. Tannert-Otto, Matthias Krüll, Norbert Suttorp, Klaus Aktories, N. Vollrath, Stefan Hippenstiel, I. Just, C. von Eichel-Streiber |
|---|---|
| Rok vydání: | 1997 |
| Předmět: |
Uridine Diphosphate Glucose
Pulmonary and Respiratory Medicine Endothelium Swine Physiology G protein Phalloidin Bacterial Toxins Clostridium difficile toxin B Biology Microfilament Filamentous actin Capillary Permeability chemistry.chemical_compound Bacterial Proteins GTP-Binding Proteins Physiology (medical) medicine Animals Cytoskeleton Cell Biology Actins Cell biology Endothelial stem cell Glucose medicine.anatomical_structure Biochemistry chemistry Endothelium Vascular Nucleotides Cyclic |
| Zdroj: | American Journal of Physiology-Lung Cellular and Molecular Physiology. 272:L38-L43 |
| ISSN: | 1522-1504 1040-0605 |
| DOI: | 10.1152/ajplung.1997.272.1.l38 |
| Popis: | The endothelial cytoskeleton is important for the regulation of endothelial barrier function. Small GTP-binding Rho proteins play a central role in the organization of the microfilament system. Clostridium difficile toxin B (TcdB) inactivates Rho proteins by glucosylation at Thr-37. We used TcdB as a probe to study the role of Rho proteins in the regulation of endothelial barrier function. TcdB time (50-170 min) and dose (10-100 ng/ml) dependently increased the hydraulic conductivity of cultured porcine pulmonary artery endothelial cell monolayers approximately 10-fold. Simultaneously, the albumin reflection coefficient decreased substantially from 0.8 to 0.15. Before endothelial hyperpermeability, TcdB reduced F-actin content in a dose-dependent manner, whereas G-actin content remained unchanged. Finally, we proved that TcdB caused dose (5-100 ng/ml)- and time-dependent glucosylation of Rho proteins in endothelial cells. Phalloidin, which stabilizes filamentous actin, prevented the effect of TcdB on endothelial permeability. In contrast to thrombin-, hydrogen peroxide-, or Escherichia coli hemolysin-induced hyperpermeability, the elevation of cyclic nucleotides did not block TcdB-related permeability. The data demonstrate a central role of small GTP-binding Rho proteins for the control of endothelial barrier function. |
| Databáze: | OpenAIRE |
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