Acidic-store depletion is required for human platelet aggregation

被引:12
作者
Ben Amor, Nidhal [2 ]
Zbidi, Hanene [2 ]
Bouaziz, Aicha [2 ,3 ]
Isaac, Jardin [1 ]
Hernandez-Cruz, Juan M. [4 ]
Salido, Gines M. [1 ]
Rosado, Juan A. [1 ]
Bartegi, Aghleb [2 ]
机构
[1] Univ Extremadura, Dept Fisiol, Cell Physiol Res Grp, Caceres 10071, Spain
[2] Inst Super Biotechnol, Unite Rech Biochim & Interact Mol, Monastir 5019, Tunisia
[3] Ctr Intermediaire Anal, Sousse, Tunisia
[4] Clin Anal Lab, Caceres, Spain
关键词
aggregation; AYPGKF; platelets; SFLLRN; TBHQ and acidic stores; thrombin; PROTEASE-ACTIVATED RECEPTOR-1; GLYCOPROTEIN-IB; DIFFERENTIAL SENSITIVITY; ACTIN POLYMERIZATION; CALCIUM-ENTRY; CA2+ ENTRY; THROMBIN; THAPSIGARGIN; RETICULUM; DISTINCT;
D O I
10.1097/MBC.0b013e32832f5104
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Platelet stimulation with thrombin induces an elevation in cytoplasmic free Ca2+ concentration ([Ca2+](c)) due to Ca2+ release from intracellular stores and entry from the extracellular medium. Two different intracellular Ca2+ stores have been described in human platelets: the dense tubular system and the lysosomal-like acidic stores. In the present study, we investigated the contribution of the acidic stores in thrombin-induced platelet aggregation. We have found that platelet aggregation induced by thrombin is reduced in a Ca2+-free medium. Discharge of the acidic Ca2+ stores by treatment with the sarcoendoplasmic Ca2+-ATPase (SERCA)3 selective inhibitor 2,5-di-(tert-butyl)-1,4-hydroquinone reduced thrombin-evoked platelet aggregation. In the presence of 2,5-di-(tert-butyl)-1,4-hydroquinone, platelet aggregation induced by the protease-activated receptor (PAR)-1 and PAR-4 agonist peptides, SFLLRN and AYPGKF, respectively, was significantly reduced. In cells with depleted acidic stores, activation of GPIb-IX-V by thrombin resulted in reduced or no platelet aggregation in a medium containing 1 mmol/l Ca2+ or in a Ca2+-free medium, respectively. This finding suggests that Ca2+ accumulation in the acidic Ca2+ compartments is required for platelet aggregation induced by activation of the G-coupled PAR-1 and PAR-4 thrombin receptors and, by the occupation of the leucine-rich glycoprotein GPIb-IX-V and provide evidence supporting a functional role of the lysosomal-like acidic Ca2+ stores in human platelets. Blood Coagul Fibrinolysis 20:511-516 (C) 2009 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.
引用
收藏
页码:511 / 516
页数:6
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