Regulation of platelet activation and thrombus formation by reactive oxygen species.

Regulation of platelet activation and thrombus formation by reactive oxygen species.
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活性氧调节血小板活化和血栓形成。

DOI:
10.1016/j.redox.2017.08.021
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发表时间:
2018-04
期刊:
影响因子:
11.4
通讯作者:
Xu K
Xu K
中科院分区:
生物学1区
文献类型:
--
作者:
Qiao J;Arthur JF;Gardiner EE;Andrews RK;Zeng L;Xu K

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活性氧(ROS)在活化的血小板中产生,在调节血小板对胶原蛋白和胶原介导的血栓形成的反应中起重要作用。作为一种主要的胶原受体,血小板特异性糖蛋白(GP)VI是免疫球蛋白(Ig)超家族的成员,具有两个细胞外Ig结构域,一个粘蛋白结构域,一个跨膜结构域和一个细胞质尾部。GPVI与Fc受体γ链(FcRγ)形成功能复合物,在受体二聚化后,通过细胞内免疫受体酪氨酸激活基元(ITAM)发出信号,导致Src家族激酶信号通路的快速激活。我们之前的研究表明,GPVI细胞质尾部的一个未配对的硫醇在配体结合的反应中迅速氧化形成GPVI同型二聚体,这表明GPVI刺激后血小板中存在氧化膜下环境。使用氧化还原敏感荧光染料(H2DCF-DA)在流式细胞术中测量细胞内ROS的变化,我们发现GPVI下游ROS的生成由两个不同的阶段组成:最初的syk非依赖性爆发,然后是额外的syk依赖性生成。在这篇综述中,我们将讨论ROS调控血小板功能的最新发现,重点关注gpvi依赖性血小板激活和血栓形成。响应配体结合的GPVI尾部硫醇的快速氧化。GPVI下游活性氧(ROS)的产生。gpvi介导的ROS生成分为syk独立期和syk依赖期。ROS在gpvi依赖性血小板活化和血栓形成中的重要作用。
Reactive oxygen species (ROS) are generated within activated platelets and play an important role in regulating platelet responses to collagen and collagen-mediated thrombus formation. As a major collagen receptor, platelet-specific glycoprotein (GP)VI is a member of the immunoglobulin (Ig) superfamily, with two extracellular Ig domains, a mucin domain, a transmembrane domain and a cytoplasmic tail. GPVI forms a functional complex with the Fc receptor γ-chain (FcRγ) that, following receptor dimerization, signals via an intracellular immunoreceptor tyrosine-based activation motif (ITAM), leading to rapid activation of Src family kinase signaling pathways. Our previous studies demonstrated that an unpaired thiol in the cytoplasmic tail of GPVI undergoes rapid oxidation to form GPVI homodimers in response to ligand binding, indicating an oxidative submembranous environment in platelets after GPVI stimulation. Using a redox-sensitive fluorescent dye (H2DCF-DA) in a flow cytometric assay to measure changes in intracellular ROS, we showed generation of ROS downstream of GPVI consists of two distinct phases: an initial Syk-independent burst followed by additional Syk-dependent generation. In this review, we will discuss recent findings on the regulation of platelet function by ROS, focusing on GPVI-dependent platelet activation and thrombus formation. Rapid oxidation of thiol in the tail of GPVI in response to ligand binding. Generation of reactive oxygen species (ROS) downstream of GPVI. GPVI-mediated ROS generation consists of syk-independent and syk-dependent phase. Important role of ROS in GPVI-dependent platelet activation and thrombus formation.
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