3-4-dihydroxyphenyllactic-acid and ferric-chloride

Protein disulfide isomerase (PDI) family members including PDI and ERp57 emerge as novel targets for anti-thrombotic treatments, but chemical agents with selectivity remain to be explored. We previously reported a novel derivative of danshensu (DSS), known as ADTM, displayed strong cardioprotective effects against oxidative stress-induced cellular injury in vitro and acute myocardial infarct in vivo. Herein, using chemical proteomics approach, we identified ERp57 as a major target of ADTM. ADTM displayed potent inhibitory effects on the redox activity of ERp57, inhibited the adenosine diphosphate (ADP)-induced expressions of P-selectin and αIIbβ3 integrin, and disrupted the interaction between ERp57 and αIIbβ3. In addition, ADTM inhibited both arachidonic acid (AA)-induced and ADP-induced platelet aggregation in vitro. Furthermore, ADTM significantly inhibited rat platelet aggregation and thrombus formation in vivo. Taken together, ADTM represents a promising candidate for anti-thrombotic therapy targeting ERp57.

Topics: Adenosine Diphosphate; Animals; Blood Platelets; Cell Adhesion Molecules; Chlorides; Disease Models, Animal; Enzyme Activation; Ferric Compounds; Fibrinolytic Agents; Gene Expression Regulation; Heme Oxygenase-1; Humans; Lactates; Microfilament Proteins; Models, Biological; P-Selectin; Phosphoproteins; Phosphorylation; Platelet Activation; Platelet Aggregation; Platelet Glycoprotein GPIIb-IIIa Complex; Protein Binding; Protein Disulfide-Isomerases; Proteomics; Rats; Thrombosis; Venous Thrombosis