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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >A mitochondria-targeted S-nitrosothiol modulates respiration, nitrosates thiols, and protects against ischemia-reperfusion injury
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A mitochondria-targeted S-nitrosothiol modulates respiration, nitrosates thiols, and protects against ischemia-reperfusion injury

机译：线粒体靶向的S-亚硝基硫醇可调节呼吸作用，亚硝化硫醇，并防止缺血再灌注损伤

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摘要

Nitric oxide (NO~*) competitively inhibits oxygen consumption by mitochondria at cytochrome c oxidase and S-nitrosates thiol proteins. We developed mitochondria-targeted S-nitrosothiols (MitoS-NOs) that selectively modulate and protect mitochondrial function. The exemplar MitoSNOI, produced by covalently linking an S-nitrosothiol to the lipophilic triphenylphosphonium cation, was rapidly and extensively accumulated within mitochondria, driven by the membrane potential, where it generated NO* and S-nitrosated thiol proteins. MitoSNOI-induced NO* production re-versibly inhibited respiration at cytochrome c oxidase and increased extracellular oxygen concentration under hypoxic conditions. MitoSNOI also caused vasorelaxation due to its NO~* generation. Infusion of MitoSNOI during reperfusion was protective against heart ischemia-reperfusion injury, consistent with a functional modification of mitochondrial proteins, such as complex I, following S-nitrosation. These results support the idea that selectively targeting NO~* donors to mitochondria is an effective strategy to reversibly modulate respiration and to protect mitochondria against ischemia-reperfusion injury.
机译：一氧化氮（NO〜*）在细胞色素c氧化酶和S-亚硝酸盐硫醇蛋白上竞争性地抑制线粒体的耗氧量。我们开发了针对线粒体的S-亚硝基硫醇（MitoS-NOs），可选择性调节和保护线粒体功能。通过将S-亚硝基硫醇与亲脂性三苯基phosph阳离子共价连接产生的示例性MitoSNOI在膜电位的驱动下迅速广泛地积累在线粒体内，并在其中产生NO *和S-亚硝化的硫醇蛋白。 MitoSNOI诱导的NO *产生可逆地抑制细胞色素C氧化酶的呼吸作用，并在缺氧条件下增加细胞外氧浓度。 MitoSNOI还由于其产生NO〜*而引起血管舒张。在再灌注过程中灌注MitoSNOI可以预防心脏缺血-再灌注损伤，这与S-亚硝化后线粒体蛋白（例如复合物I）的功能修饰一致。这些结果支持这样的想法，即选择性地将NO-*供体靶向线粒体是一种可逆地调节呼吸并保护线粒体免受缺血-再灌注损伤的有效策略。

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  • 作者

    Tracy A. Prime; Frances H. Blaikie; Cameron Evans; Sergiy M. Nadtochiy; Andrew M. James; Christina C. Dahm; Dario A. Vitturi; Rakesh P. Patel; C. Robin Hiley; Irina Abakumova; Raquel Requejo; Edward T. Chouchani; Thomas R. Hurd; John F. Garvey; Cormac T. Taylor; Paul S. Brookes; Robin A. J. Smith; Michael P. Murphy;

  • 作者单位

    MRC Mitochondrial Biology Unit, Hills Road, Cambridge CB2 0XY, United Kingdom;

    Department of Chemistry, University of Otago, P. O. Box 56, Dunedin 9054, New Zealand;

    Department of Chemistry, University of Otago, P. O. Box 56, Dunedin 9054, New Zealand;

    Department of Anesthesiology, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642;

    MRC Mitochondrial Biology Unit, Hills Road, Cambridge CB2 0XY, United Kingdom;

    MRC Mitochondrial Biology Unit, Hills Road, Cambridge CB2 0XY, United Kingdom;

    Department of Pathology and Center for Free Radical Biology, University of Alabama at Birmingham, 901 19th Street South, Birmingham, AL 35294;

    Department of Pathology and Center for Free Radical Biology, University of Alabama at Birmingham, 901 19th Street South, Birmingham, AL 35294;

    Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge CB2 1PD, United Kingdom;

    MRC Mitochondrial Biology Unit, Hills Road, Cambridge CB2 0XY, United Kingdom;

    MRC Mitochondrial Biology Unit, Hills Road, Cambridge CB2 0XY, United Kingdom;

    MRC Mitochondrial Biology Unit, Hills Road, Cambridge CB2 0XY, United Kingdom;

    MRC Mitochondrial Biology Unit, Hills Road, Cambridge CB2 0XY, United Kingdom;

    Conway Institute, University College, Dublin, Dublin 4, Ireland;

    Conway Institute, University College, Dublin, Dublin 4, Ireland;

    Department of Anesthesiology, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642;

    Department of Chemistry, University of Otago, P. O. Box 56, Dunedin 9054, New Zealand;

    MRC Mitochondrial Biology Unit, Hills Road, Cambridge CB2 0XY, United Kingdom;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    nitric oxide; S-nitrosation;

    机译：一氧化氮;亚硝化;

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