Tuyển tập báo cáo các nghiên cứu khoa học quốc tế ngành hóa học dành cho các bạn yêu hóa học tham khảo đề tài: Rac1-mediated signaling plays a central role in secretion-dependent platelet aggregation in human blood stimulated by atherosclerotic plaque | Dwivedi et al. Journal of Translational Medicine 2010 8 128 http content 8 1 128 TRANSLATIONAL MEDICINE RESEARCH Open Access Rac1-mediated signaling plays a central role in secretion-dependent platelet aggregation in human blood stimulated by atherosclerotic plaque 1 13 1 2 1 Suman Dwivedi Dharmendra Pandey Anna L Khandoga Richard Brandl Wolfgang Siess Abstract Background Platelet activation requires rapid remodeling of the actin cytoskeleton which is regulated by small GTP-binding proteins. By using the Rac1-specific inhibitor NSC23766 we have recently found that Rac1 is a central component of a signaling pathway that regulates dephosphorylation and activation of the actin-dynamising protein cofilin dense and a-granule secretion and subsequent aggregation of thrombin-stimulated washed platelets. Objectives To study whether NSC23766 inhibits stimulus-induced platelet secretion and aggregation in blood. Methods Human platelet aggregation and ATP-secretion were measured in hirudin-anticoagulated blood and platelet-rich plasma PRP by using multiple electrode aggregometry and the Lumi-aggregometer. Platelet P-selectin expression was quantified by flow cytometry. Results NSC23766 300 gM inhibited TRAP- collagen- atherosclerotic plaque- and ADP-induced platelet aggregation in blood by and 70 respectively. The IC50 values for inhibition of TRAP- collagen- and atherosclerotic plaque- were 50 18 gM 64 35 gM and 50 30 gM NSC23766 mean SD n 3-7 respectively. In blood containing RGDS to block integrin aIIbp3-mediated platelet aggregation NSC23766 300 gM completely inhibited P-selectin expression and reduced ATP-secretion after TRAP and collagen stimulation by 73 and 85 respectively. In ADP-stimulated PRP NSC23766 almost completely inhibited P-selectin expression in contrast to aspirin which was ineffective. Moreover NSC23766 300 gM decreased plaque-stimulated platelet adhesion aggregate formation under arterial flow conditions .
