Zinc Modulates the Interaction of Protein C and Activated Protein C with Endothelial Cell Protein C Receptor

Activated protein C inhibits bisphosphonate-induced endothelial cell death via the endothelial protein C receptor and nuclear factor-κB pathways.

Bisphosphonates promote apoptosis of cancer cells as well as osteoclasts in bone metastatic sites, but several clinical trials and high concentration treatment have shown that bisphosphonates have side effects that include bone loss and damage to normal cells. The aim of this study was to elucidate the protective effect and the possible mechanism of activated protein C (APC) against bisphosphon...

Interaction of activated protein C with serpins.

The inhibition of activated protein C by six different serine protease inhibitors (serpins) that have arginine residues in the P1 position has been investigated. Micromolar concentrations of C1-inhibitor failed to inhibit the enzyme, and it was inhibited only slowly by antithrombin III with an association rate constant (kass.) of 0.15 M-1.s-1. The kass. values for the other serpins tested (prot...

Factor X binding to endothelial cell protein C receptor: comparison with factor VIIa and activated protein C.

The endothelial cell protein C receptor augments protein C activation by the thrombin-thrombomodulin complex.

Protein C activation on the surface of the endothelium is critical to the negative regulation of blood coagulation. We now demonstrate that monoclonal antibodies that block protein C binding to the endothelial cell protein C receptor (EPCR) reduce protein C activation rates by the thrombin-thrombomodulin complex on endothelium, but that antibodies that bind to EPCR without blocking protein C bi...

Inhibition of staurosporine-induced apoptosis of endothelial cells by activated protein C requires protease-activated receptor-1 and endothelial cell protein C receptor.

In a model of staurosporine-induced apoptosis using EAhy926 endothelial cells, inhibition of apoptosis by activated protein C was dose-dependent and required the enzyme's active site, implicating activated protein C-mediated proteolysis. Consistent with this implication, both protease-activated receptor-1 (PAR-1) and endothelial cell protein C receptor (EPCR) were required for the anti-apoptoti...