کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10751526 | 1050314 | 2015 | 7 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
A tryptophan derivative TD-26 attenuates thrombus formation by inhibiting both PI3K/Akt signaling and binding of fibrinogen to integrin αIIbβ3
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: A tryptophan derivative TD-26 attenuates thrombus formation by inhibiting both PI3K/Akt signaling and binding of fibrinogen to integrin αIIbβ3 A tryptophan derivative TD-26 attenuates thrombus formation by inhibiting both PI3K/Akt signaling and binding of fibrinogen to integrin αIIbβ3](/preview/png/10751526.png)
چکیده انگلیسی
The incidence and mortality of thrombotic disorders are rapidly increasing worldwide. The existing antithrombotic drugs, however, are associated with side effects, especially bleeding complications. Therefore, there remains a need for the development of more effective and safer antithrombotic agents. In this study, we discovered a new synthetic tryptophan derivative TD-26, producing potent inhibitory effect on platelet aggregation while without causing obvious bleeding risk. It has been shown that TD-26 inhibited platelet aggregation induced by ADP, thrombin, U46619 and collagen in vitro and suppressed the platelet aggregation induced by ADP ex vivo. Mechanism studies indicated that TD-26 inhibited platelet adhesion to fibrinogen-coated surfaces, blocked the binding of fibrinogen to integrin αIIbβ3 and reduced AktSer473 phosphorylation in platelet phosphatidylinositol 3-kinase (PI3K) signaling. Furthermore, TD-26 exhibited potent antithrombotic activity in vivo. In animal models, it decreased death of mice with acute pulmonary thrombosis by 90% and attenuated thrombosis weight by 60.3%, both at a dose of 3 mg/kg. Additionally, TD-26 did not obviously prolong bleeding time in mice. Taken together, our results reveal that TD-26 is a novel antithrombotic compound exhibiting both integrin αIIbβ3 inhibition and PI3K signaling blockage, with a low bleeding risk.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 465, Issue 3, 25 September 2015, Pages 516-522
Journal: Biochemical and Biophysical Research Communications - Volume 465, Issue 3, 25 September 2015, Pages 516-522
نویسندگان
Yahui Chen, Ying Wang, Zhouling Xie, Xin Ming, Zhiyu Li, Yi Kong,