Mutagenesis studies toward understanding the intracellular signaling mechanism of antithrombin.

ABSTRACT:

Summary background

Recent studies have indicated that antithrombin (AT) possesses both anti-inflammatory and antiangiogenic properties.

Objectives

The purpose of this study was to investigate the mechanism of the intracellular signaling activities of AT using wild-type and mutant serpins that have reduced anticoagulant activities due to mutations in either the reactive center loop (RCL) or the heparin-binding site.

Methods

Direct cellular effects of the AT derivatives were compared in the LPS-stimulated endothelial cells by employing permeability and neutrophil adhesion assays in the absence and presence of pertussis toxin (PTX) and siRNAs for either syndecan-4 or sphingosine 1-phosphate receptor 1 (S1P(1)). Furthermore, the roles of prostacyclin and nuclear factor (N

SUBMITTER: Bae JS 

PROVIDER: S-EPMC2720322 | biostudies-literature | 2009 May

REPOSITORIES: biostudies-literature