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Báo cáo hóa học: "Rac1-mediated signaling plays a central role in secretion-dependent platelet aggregation in human blood stimulated by atherosclerotic plaque"

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 www.translational-medicine.eom 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 95.1 93.4 92.6 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 .