Reeder Brandon J, Svistunenko Dimitri A, Cooper Christopher E, Wilson Michael T
Department of Biological Sciences, University of Essex, Wivenhoe Park, Colchester, Essex, UK.
Antioxid Redox Signal. 2004 Dec;6(6):954-66. doi: 10.1089/ars.2004.6.954.
Recent research has shown that myoglobin and hemoglobin play important roles in the pathology of certain disease states, such as renal dysfunction following rhabdomyolysis and vasospasm following subarachnoid hemorrhages. These pathologies are linked to the interaction of peroxides with heme proteins to initiate oxidative reactions, including generation of powerful vasoactive molecules (the isoprostanes) from free and membrane- bound lipids. This review focuses on the peroxide-induced formation of radicals, their assignment to specific protein residues, and the pseudoperoxidase and prooxidant activities of the heme proteins. The discovery of heme to protein cross-linked forms of myoglobin and hemoglobin in vivo, definitive markers of the participation of these heme proteins in oxidative reactions, and the recent results from heme oxygenase knockout/knockin animal model studies, indicate that higher oxidation states (ferryl) of heme proteins and their associated radicals play a major role in the mechanisms of pathology.
近期研究表明，肌红蛋白和血红蛋白在某些疾病状态的病理过程中发挥着重要作用，例如横纹肌溶解后的肾功能障碍以及蛛网膜下腔出血后的血管痉挛。这些病理情况与过氧化物和血红素蛋白的相互作用引发氧化反应有关，包括从游离和膜结合脂质中生成强大的血管活性分子（异前列腺素）。本综述聚焦于过氧化物诱导的自由基形成、它们在特定蛋白质残基上的定位，以及血红素蛋白的伪过氧化物酶和促氧化活性。在体内发现肌红蛋白和血红蛋白的血红素与蛋白质交联形式，这是这些血红素蛋白参与氧化反应的确切标志物，以及血红素加氧酶基因敲除/敲入动物模型研究的最新结果表明，血红素蛋白的较高氧化态（高铁血红素）及其相关自由基在病理机制中起主要作用。
