Suppression of Human Platelet Activation via Integrin αIIbβ3 Outside-In Independent Signal and Reduction of the Mortality in Pulmonary Thrombosis by Auraptene

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题名:	Suppression of Human Platelet Activation via Integrin αIIbβ3 Outside-In Independent Signal and Reduction of the Mortality in Pulmonary Thrombosis by Auraptene
作者:	Hsia, Chih-Wei;Tsai, Cheng-Lin;Sheu, Joen-Rong;Lu, Wan-Jung;Hsia, Chih-Hsuan;Velusamy, Marappan;Jayakumar, Thanasekaran;Li, Jiun-Yi
贡献者:	視光學系
关键词:	auraptene;human platelet;arterial thrombosis;ERK1/2/JNK1/2;experimental mice
日期:	2019-11-01
上传时间:	2025-08-11 14:44:25 (UTC+8)
摘要:	Auraptene is the most abundant coumarin derivative from plants. The pharmacological value of this compound has been well demonstrated, especially in the prevention of cancer and neurodegenerative diseases. Platelet activation is a major factor contributing to arterial thrombosis. Thus, this study evaluated the influence of auraptene in platelet aggregation and thrombotic formation. Auraptene inhibited platelet aggregation in human platelets stimulated with collagen only. However, auraptene was not effective in inhibiting platelet aggregation stimulated with thrombin, arachidonic acid, and U46619. Auraptene also repressed ATP release, [Ca2+]i mobilization, and P-selectin expression. Moreover, it markedly blocked PAC-1 binding to integrin αIIbβ3. However, it had no influence on properties related to integrin αIIbβ3-mediated outside-in signaling, such as the adhesion number, spreading area of platelets, and fibrin clot retraction. Auraptene inhibited the phosphorylation of Lyn-Fyn-Syk, phospholipase Cγ2 (PLCγ2), protein kinase C (PKC), Akt, and mitogen-activated protein kinases (MAPKs; extracellular-signal-regulated kinase (ERK1/2), and c-Jun N-terminal kinase (JNK1/2), but not p38 MAPK). Neither SQ22536, an adenylate cyclase inhibitor, nor ODQ, a guanylate cyclase inhibitor, reversed the auraptene-mediated inhibition of platelet aggregation. Auraptene reduced mortality caused by adenosine diphosphate (ADP)-induced pulmonary thromboembolism. In conclusion, this study provides definite evidence that auraptene signifies a potential therapeutic agent for preventing thromboembolic disorders.
關聯:	International Journal of Molecular Sciences, 20(22), 5585. https://doi.org/10.3390/ijms20225585
显示于类别:	[視光學系] 期刊論文

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