کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8530002 | 1558865 | 2017 | 25 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
The novel compound MP407 inhibits platelet aggregation through cyclic AMP-dependent processes
دانلود مقاله + سفارش ترجمه
دانلود مقاله ISI انگلیسی
رایگان برای ایرانیان
کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
علوم اعصاب سلولی و مولکولی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: The novel compound MP407 inhibits platelet aggregation through cyclic AMP-dependent processes The novel compound MP407 inhibits platelet aggregation through cyclic AMP-dependent processes](/preview/png/8530002.png)
چکیده انگلیسی
Platelet hyperactivity plays a critical role for initiating several vascular diseases such as atherothrombosis. Therefore, development of effective antiplatelet agents is necessary for ameliorating platelet-related diseases. In this study, we investigated the effects of the new synthesized compound, MP407 on platelet aggregation and further elucidated the underlying mechanisms. Our results demonstrated that MP407 dose-dependently inhibited collagen-induced platelet aggregation, thromboxane B2 (TXB2) production, intracellular Ca2+ mobilization, platelet membrane GPIIb/IIIa expression, and the phosphorylation of Akt, GSK3β, p38MAPK, and phospho (Ser) PKC substrate (p47). Moreover, MP407 is able to increase the cyclic AMP formation both in resting and activated platelets. However, blocking cyclic AMP formation with 2â²5â²-ddAdo, an inhibitor of adenylate cyclase, greatly reversed the antiplatelet activity of MP407 and related platelet-activating pathways. MP407 also enhanced VASP phosphorylation at Ser157 in collagen-stimulated platelets, which was attenuated by addition of 2â²5â²-ddAdo. Therefore, the antiplatelet activity of MP407 may be modulated by cyclic AMP-dependent regulation of Akt, GSK3β, p38MAPK and VASP phosphorylation. Notably, treatment with MP407 markedly reduced the pulmonary thrombosis and the numbers of paralysis and death in mice induced by ADP injection, but did not affect the bleeding time. Taken together, MP407 may be a potential candidate or lead compound for developing novel antiplatelet or antithrombotic agents for platelet hyperactivity-triggered disease therapy.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Journal of Pharmacology - Volume 815, 15 November 2017, Pages 324-331
Journal: European Journal of Pharmacology - Volume 815, 15 November 2017, Pages 324-331
نویسندگان
Chung-Shuen Lin, Tso-Hsiao Chen, I-Hsin Lin, An-Rong Lee, Tz-Chong Chou,