Spatially distinct production of reactive oxygen species regulates platelet activation
Spatially distinct production of reactive oxygen species regulates platelet activation
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DOI：
10.1016/j.freeradbiomed.2008.03.021
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发表时间：
2008-07-15
影响因子：
7.4
通讯作者：
Williams, Mark S.
中科院分区：
文献类型：
--
作者：
Bakdash, Nadia;Williams, Mark S.
血小板在止血中起关键作用，已知氧化还原平衡的变化会改变血小板活化和聚集。有趣的是，血小板的活化导致活性氧（ROS）的产生，但这些ROS的作用仍不清楚。使用流式细胞术和化学发光，激动剂诱导的ROS生成被发现是空间上不同的刺激，通过主要的胶原蛋白受体GPVI诱导血小板内ROS，而凝血酶诱导细胞外ROS的生产。由GPVI选择性激动剂惊厥素或凝血酶引起的血小板活化受ROS产生的不同调节。因此，表面表达的CD 62 P，CD 40 L，或激活的整合素α IIb β 3被废除的药理抗氧化剂，但磷脂酰丝氨酸的外化没有受到抑制。此外，细胞外抗氧化剂SOD/过氧化氢酶显着抑制凝血酶，但不惊厥素，诱导的CD 62 P表达和α IIb β 3激活。这些数据表明，ROS选择性地调节血小板活化中的生化步骤，并且ROS的不同来源和离散的氧化还原敏感性途径可能控制响应于GPVI或凝血酶刺激的血小板活化。因此，靶向活性氧与位点特异性抗氧化剂可以通过凝血酶或胶原蛋白差异调节血小板活化。(C)2008年爱思唯尔公司All rights reserved.
Platelets play a key role in hemostasis and changes in redox balance are known to alter platelet activation and aggregation. Interestingly, activation of platelets leads to production of reactive oxygen species (ROS), but the role(s) of these ROS remain unclear. Using flow cytometry and chemiluminescence, agonist-induced ROS generation was found to be spatially distinct with stimulation through the major collagen receptor GPVI inducing only intraplatelet ROS while thrombin induced production of extracellular ROS. Platelet activation by either the GPVI-selective agonist convulxin or thrombin was differentially regulated by ROS generation. Thus, surface expression of CD62P, CD40L, or activated integrin alpha IIb beta 3 was abrogated by pharmacologic antioxidants but externalization of phosphatidylserine was not inhibited. Furthermore, extracellular antioxidants SOD/catalase markedly inhibited thrombin-, but not convulxin-, induced CD62P expression and alpha IIb beta 3 activation. The data suggest that ROS selectively regulate biochemical steps in platelet activation and that distinct source(s) of ROS and discrete redox-sensitive pathway(s) may control platelet activation in response to GPVI or thrombin stimulation. Thus, targeting ROS with site-specific antioxidants may differentially regulate platelet activation via thrombin or collagen. (C) 2008 Elsevier Inc. All rights reserved.