کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1926120 1536447 2009 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
STIM1, Orai1 and hTRPC1 are important for thrombin- and ADP-induced aggregation in human platelets
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
STIM1, Orai1 and hTRPC1 are important for thrombin- and ADP-induced aggregation in human platelets
چکیده انگلیسی

Ca2+ entry, particularly store-operated Ca2+ entry (SOCE), has been reported to be crucial for a variety of cellular functions. SOCE is a mechanism regulated by the Ca2+ content of the stores, where the intraluminal Ca2+ sensor STromal Interaction Molecule 1 (STIM1) has been reported to communicate the filling state of the intracellular Ca2+ stores to the store-operated Ca2+-permeable channels in the plasma membrane, likely involving Orai1 and TRPC proteins, such as TRPC1. Here we have investigated the role of Orai1, STIM1 and TRPC1 in platelet aggregation, an event that occurs during the process of thrombosis and hemostasis. Electrotransjection of cells with anti-STIM1 (25–139) antibody, directed towards the Ca2+-binding motif, significantly reduced thrombin-induced aggregation and prevented ADP-evoked response. Extracellular application of the anti-STIM1 antibody, in order to block the function of plasma membrane-located STIM1, reduced thrombin- and ADP-stimulated platelet aggregation to a lesser extent. Introduction of an anti-Orai1 (288–301) antibody, which binds the STIM1-binding site located in the Orai1 C-terminus, or extracellular application of anti-hTRPC1 (557–571) antibody to impair hTRPC1 channel function, significantly reduced thrombin- and ADP-induced platelet aggregation. These findings suggest a role of STIM1, Orai1 and hTRPC1 in thrombin- and ADP-induced platelet aggregation probably through the regulation of Ca2+ entry, which might become targets for the development of therapeutic strategies to treat platelet hyperactivity and thrombosis disorders.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Archives of Biochemistry and Biophysics - Volume 490, Issue 2, 15 October 2009, Pages 137–144
نویسندگان
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