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Zinc regulates reactive oxygen species generation in platelets

机译：锌调节血小板中的活性氧物种

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摘要

Vascular complications resulting from atherosclerosis development are a major cause of death. Reactive oxygen species (ROS) are produced by platelets during activation, and have been demonstrated to positively regulate platelet activatory responses. Zn2+ is also an important hemostatic cofactor in platelets, acting both as a platelet agonist and second messenger. Whilst the effect of Zn2+-dependent signaling mechanisms on ROS production in nucleated cells has been demonstrated, comparable roles in platelets have yet to be investigated. In this study we investigated the relationship between fluctuations in cytosolic Zn-2 [Zn2+](i) and platelet ROS production. Agonist-evoked ROS production, GSH levels and GPx activity are abrogated in platelets treated with the Zn2+-chelator, TPEN. Conversely, increasing platelet [Zn2+](i) using Zn2+ ionophores potentiated ROS generation and decreased GSH levels and GPx activity. Zn2+-dependent ROS production was sensitive to pretreatment with DPI or mitoTEMPO, NADPH oxidase and mitochondria inhibitors respectively. Increasing [Zn2+](i) resulted in increases of Erk1/2 and JNK phosphorylation. Our data are consistent with a functional association between [Zn2+](i) and ROS production in platelets that could influence thrombus formation in a clinical context.
机译：动脉粥样硬化发展引起的血管并发症是死亡的主要原因。活性氧（ROS）在活化过程中由血小板产生，并已被证明能积极调节血小板活化反应。Zn2+也是血小板中重要的止血辅助因子，同时作为血小板激动剂和第二信使发挥作用。虽然Zn2+依赖的信号机制对有核细胞中ROS产生的影响已被证实，但血小板中类似的作用仍有待研究。在这项研究中，我们研究了细胞溶质Zn-2[Zn2+]（i）的波动与血小板ROS产生之间的关系。在用Zn2+螯合剂TPEN处理的血小板中，激动剂诱发的ROS产生、GSH水平和GPx活性被消除。相反，使用Zn2+离子载体增加血小板[Zn2+]（i）可增强ROS生成，降低GSH水平和GPx活性。Zn2+依赖的活性氧生成分别对DPI或mitoTEMPO、NADPH氧化酶和线粒体抑制剂的预处理敏感。增加[Zn2+]（i）导致Erk1/2和JNK磷酸化增加。我们的数据与[Zn2+]（i）和血小板中ROS生成之间的功能关联一致，在临床环境中，这可能会影响血栓的形成。

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  • 来源
    《Platelets》 |2021年第3期|共10页
  • 作者

    Lopes-Pires M. E.; Ahmed N. S.; Vara D.; Gibbins J. M.; Pula G.; Pugh N.;

  • 作者单位

    Anglia Ruskin Univ Sch Life Sci East Rd Cambridge CB1 1PT England;

    Anglia Ruskin Univ Sch Life Sci East Rd Cambridge CB1 1PT England;

    Univ Exeter Coll Med &

    Hlth Exeter Devon England;

    Univ Reading Sch Biol Sci Inst Cardiovasc &

    Metab Res Reading Berks England;

    Univ Med Ctr Eppendorf Hamburg Inst Clin Chem &

    Lab Med Hamburg Germany;

    Anglia Ruskin Univ Sch Life Sci East Rd Cambridge CB1 1PT England;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 基础医学;
  • 关键词

    Platelets; ROS; signal transduction; thrombosis; Zinc;

    机译：血小板;ROS;信号转导;血栓形成;锌;

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