4 research outputs found
Bioaktivu mazmolekularo NO-induktoru un donoru sinteze un izpete
Available from Latvian Academic Library / LAL - Latvian Academic LibrarySIGLELVLatvi
Protein disulfide isomerase-A1 regulates intraplatelet reactive oxygen speciesthromboxane A<SUB>2</SUB>-dependent pathway in human platelets
BACKGROUND: Plateletâderived protein disulfide isomerase 1 (PDIA1) regulates thrombus formation, but its role in the regulation of platelet function is not fully understood. AIMS: The aim of this study was to characterize the role of PDIA1 in human platelets. METHODS: Proteomic analysis of PDI isoforms in platelets was performed using liquid chromatography tandem mass spectometry, and the expression of PDIs on platelets in response to collagen, TRAPâ14, or ADP was measured with flow cytometry. The effects of bepristat, a selective PDIA1 inhibitor, on platelet aggregation, expression of platelet surface activation markers, thromboxane A(2) (TxA(2)), and reactive oxygen species (ROS) generation were evaluated by optical aggregometry, flow cytometry, ELISA, and dihydrodichlorofluorescein diacetateâbased fluorescent assay, respectively. RESULTS: PDIA1 was less abundant compared with PDIA3 in resting platelets and platelets stimulated with TRAPâ14, collagen, or ADP. Collagen, but not ADP, induced a significant increase in PDIA1 expression. Bepristat potently inhibited the aggregation of washed platelets induced by collagen or convulxin, but only weakly inhibited platelet aggregation induced by TRAPâ14 or thrombin, and had the negligible effect on platelet aggregation induced by arachidonic acid. Inhibition of PDIA1 by bepristat resulted in the reduction of TxA(2) and ROS production in collagenâ or thrombinâstimulated platelets. Furthermore, bepristat reduced the activation of αIIbÎČ3 integrin and expression of Pâselectin. CONCLUSIONS: PDIA1 acts as an intraplatelet regulator of the ROSâTxA(2) pathway in collagenâGP VI receptorâmediated platelet activation that is a mechanistically distinct pathway from extracellular regulation of αIIbÎČ3 integrin by PDIA3
Aziridine-2-carboxylic acid derivatives and its open-ring isomers as a novel PDIA1 inhibitors
Acyl derivatives of aziridine-2-carboxylic acid have been synthesized and tested as PDIA1 inhibitors. Calculations of charge value and distribution in aziridine ring system and some alkylating agents were performed. For the first time was found that acyl derivatives of aziridine-2-carboxylic acid are weak to moderately active PDIA1 inhibitors
Comparison of anti-cancer effects of novel protein disulphide isomerase (PDI) inhibitors in breast cancer cells characterized by high and low PDIA17 expression
Protein disulphide isomerases (PDIs) play an important role in cancer progression. However, the relative contribution of the various isoforms of PDI in tumorigenesis is not clear