血小板与钙离子信号的研究进展
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摘要
激动剂诱导细胞内钙离子浓度升高是血小板活化止血和血栓形成的必要条件,它是通过细胞内钙离子释放和质膜内钙离子进入而发生的。Ca2+库释放是一种行之有效的过程,首先磷脂酶(PL)C产生肌醇-1,4,5-三磷酸肌醇(IP3),进而通过IP3通道受体释放细胞内储存的Ca2+,从而完成Ca2+释放。在血小板活化过程中钙离子浓度明显升高有助于活化的各个步骤。钙离子作为细胞的第二信使,参与大多数的生物活动过程,尤其在细胞内钙池引发的钙离子的进入(store-operated Ca2+entry,SOCE)在血小板激活过程中发挥着重要的作用。血小板在血管内激活极易引起血栓,因此研究血小板活化机理可能会对某些疾病的治疗起到关键作用。
Agonist-induced elevation in cytosolic Ca2+concentrations is essential for platelet activation in hemostasis and thrombosis.It occurs through Ca2+release from intracellular stores and Ca2+entry through the plasma membrane(PM).Ca2+store release is a well-established process involving phospholipase(PL)C-mediated production of inositol-1,4,5-trisphosphate(IP3),which in turn releases Ca2+from the intracellular stores through IP3 receptor channels.During the course of platelet activation,the increase of Ca2+concentration contributes to each step of the activation.As the second messenger of cells,Ca2+is involved in most biological processes.Especially,store-operated calcium entry(SOCE)plays an important role in the activation of platelets.The activation of platelets in the blood vessels is very likely to cause thrombus,so the study of the mechanism of platelet activation may play a key role in the treatment of certain diseases.
Agonist-induced elevation in cytosolic Ca2+concentrations is essential for platelet activation in hemostasis and thrombosis.It occurs through Ca2+release from intracellular stores and Ca2+entry through the plasma membrane(PM).Ca2+store release is a well-established process involving phospholipase(PL)C-mediated production of inositol-1,4,5-trisphosphate(IP3),which in turn releases Ca2+from the intracellular stores through IP3 receptor channels.During the course of platelet activation,the increase of Ca2+concentration contributes to each step of the activation.As the second messenger of cells,Ca2+is involved in most biological processes.Especially,store-operated calcium entry(SOCE)plays an important role in the activation of platelets.The activation of platelets in the blood vessels is very likely to cause thrombus,so the study of the mechanism of platelet activation may play a key role in the treatment of certain diseases.
引文
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[22] Bergmeier W,Stefanini L.Novel molecules in calcium signaling in platelets[J].J Thromb Haemost,2009,7(S1):187-190.
[23] Zhou Y,Cai X,Nwokonko R M,et al.The STIM-Orai coupling interface and gating of the Orai1channel[J].Cell Calcium,2017,63:8.
[24] Kile B T.The role of apoptosis in megakaryocytes and platelets[J].Br J Haematol,2014,165(2):217.
[25] Moissoglu K,Kiessling V,Wan C,et al.Regulation of Rac1translocation and activation by membrane domains and their boundaries[J].J Cell Sci,2014,127(11):2565-2576.
[2] Whyte C S,Mitchell J L,Mutch N J.Platelet-mediated modulation of fibrinolysis[J].Semin Thromb Hemost,2017,43(02):115-128.
[3]王颖,董树旭,赵轼轩,等.巨核细胞发育和血小板形成的形态结构[J].中国冶金工业医学杂志,2015,32(1):15-16.
[4] Naeim F,Rao P N,Song S X,et al.Disorders of megakaryocytes and platelets.[M].In:Atlas of Hematopathology.Los Angeles:University of California,2008:705-714.DOI:10.1016/B978-0-12-385183-3.00062-0.
[5]韦昌青.P2Y12受体抑制剂的合成及其抗血小板聚集活性研究[D].上海:第二军医大学,2013.
[6] Flierl U,Htun N M,Peter K.Clotting mechanisms and haemophilias[M].In:Oxford Textbook of Vascular Surgery,2016:58-66.DOI:10.1093/med/9780199658220.003.0006.
[7] Heemskerk J W M,Cosemans J M E M,Meijden P E J V D.Platelets and Coagulation[M].Platelets in Thrombotic and Non-Thrombotic Disorders:Springer International Publishing,2017.
[8] Berridge M J.The inositol trisphosphate/calcium signaling pathway in health and disease[J].Physiol Rev,2016,96(4):1261-1296.
[9] Albarran L,Lopez J J,Amor N B,et al.Dynamic interaction of SARAF with STIM1and Orai1to modulate store-operated calcium entry[J].Sci Rep,2016,6:24452.
[10] Gwack Y,Srikanth S,Ohhora M,et al.Hair loss and defective T-and B-cell function in mice lacking ORAI1[J].Mol Cell Biol,2008,28(17):5209-5222.
[11] Hirve N,Rajanikanth V,Hogan P G,et al.Coiled-coil formation conveys a STIM1signal from ER lumen to cytoplasm[J].Cell Rep,2018,22(1):72.
[12] Stathopulos P B,Zheng L,Li G Y,et al.Structural and mechanistic insights into STIM1-mediated initiation of store-operated calcium entry[J].Cell,2008,135(1):110-122.
[13] Williams R T,Manji S S,Parker N J,et al.Identification and characterization of the STIM(stromal interaction molecule)gene family:coding for a novel class of transmembrane proteins[J].Biochem J,2001,357(Pt3):673.
[14]颜红柱,钟南哲,李维卿,等.ATP2A2通过钙离子浓度变化参与肿瘤发生机制的研究进展[J].第二军医大学学报,2013,34(11):1248-1252.
[15] Tuusa J T,Markkanen P M H,Apaja P M,et al.The endoplasmic reticulum Ca2+-pump SERCA2binteracts with G protein-coupled receptors and enhances their expression at the cell surface[J].J Mol Biol,2007,371(3):622.
[16] Clemens R A,Lowell C A.Store-operated calcium signaling in neutrophils[J].J Leukoc Biol,2015,98(4):497.
[17] Vargaszabo D,Pleines I,Nieswandt B.Cell adhesion mechanisms in platelets[J].Arterioscler Thromb Vasc Biol,2008,28(3):403.
[18] Liu G,Liu G,Alzoubi K,et al.Upregulation of store operated Ca channel Orai1,stimulation of Ca(2+)entry and triggering of cell membrane scrambling in platelets by mineralocorticoid DOCA[J].Kidney Blood Press Res,2013,38(1):21-30.
[19] Mukherjee S,Karolak A,Debant M,et al.Molecular dynamics simulations of membrane bound STIM1to investigate conformational changes during STIM1activation upon calcium release[J].J Chem Inf Model,2017,57(2):335-344.
[20] Yeung P S,Yamashita M,Prakriya M.Pore opening mechanism of CRAC channels[J].Cell Calcium,2017,63:14-19.
[21] Mahautsmith M P.A role for platelet TRPC channels in the Ca2+response that induces procoagulant activity[J].Sci Signal,2013,6(281):pe23.
[22] Bergmeier W,Stefanini L.Novel molecules in calcium signaling in platelets[J].J Thromb Haemost,2009,7(S1):187-190.
[23] Zhou Y,Cai X,Nwokonko R M,et al.The STIM-Orai coupling interface and gating of the Orai1channel[J].Cell Calcium,2017,63:8.
[24] Kile B T.The role of apoptosis in megakaryocytes and platelets[J].Br J Haematol,2014,165(2):217.
[25] Moissoglu K,Kiessling V,Wan C,et al.Regulation of Rac1translocation and activation by membrane domains and their boundaries[J].J Cell Sci,2014,127(11):2565-2576.