Giustarini Daniela, Dalle-Donne Isabella, Cavarra Eleonora, Fineschi Silvia, Lungarella Giuseppe, Milzani Aldo, Rossi Ranieri
Department of Neurosciences, Pharmacology Unit, University of Siena, Via A. Moro 4, 53100 Siena, Italy.
Biochem Pharmacol. 2006 Jun 14;71(12):1753-64. doi: 10.1016/j.bcp.2006.03.015. Epub 2006 Mar 24.
Haemoglobins bearing reactive sulfhydryl groups have been shown to be able to interplay with glutathione in some detoxification processes. Blood from different mouse strains commonly used as experimental animal models, i.e., C57, DBA and ICR, was treated with oxidants with the aim of evaluating: (i) the involvement of protein SH groups in oxido-reductive reactions that are commonly carried out by glutathione and (ii) the impact of this phenomenon on blood-mediated metabolism of thiol reactants. All the main forms of glutathione (reduced, disulfide, and mixed disulfide with haemoglobin) were measured after oxidant treatment. Significant differences were found among the studied strains: DBA mice formed preferably mixed disulfides instead of glutathione disulfide, whereas the opposite behaviour was shown by C57 mice. Unexpectedly, the ICR strain resulted to be composed of three different subgroups (ICRa, ICRb, and ICRc), with the ICRa behaving similarly to the DBA strain, ICRc to the C57 strain, and ICRc showing an intermediate behaviour. These results are due to the different number of haemoglobin SH groups in the studied mouse strains. In particular, additional fast-reacting SH groups were found in haemoglobin from DBA, ICRa, and ICRb mice, but not in the C57 and ICRc strain. These differences were also reflected in the susceptibility of haemoglobin to dimerize and in its ability to react with S-nitrosocysteine. Because of the widely different reactivity of haemoglobin cysteinyl residues, the mouse strains examined are an interesting but complicated model in which to study the pharmacological and toxicological action of some drugs.
已证明带有反应性巯基的血红蛋白能够在某些解毒过程中与谷胱甘肽相互作用。以常用作实验动物模型的不同小鼠品系(即C57、DBA和ICR)的血液为研究对象,用氧化剂进行处理,目的是评估:(i)蛋白质巯基在通常由谷胱甘肽进行的氧化还原反应中的参与情况,以及(ii)这一现象对血液介导的硫醇反应物代谢的影响。在氧化剂处理后,对谷胱甘肽的所有主要形式(还原型、二硫键型以及与血红蛋白形成的混合二硫键型)进行了测定。在所研究的品系之间发现了显著差异:DBA小鼠更倾向于形成混合二硫键而非谷胱甘肽二硫键,而C57小鼠则表现出相反的行为。出乎意料的是,ICR品系由三个不同的亚组(ICRa、ICRb和ICRc)组成,其中ICRa的行为与DBA品系相似,ICRc与C57品系相似,而ICRb表现出中间行为。这些结果归因于所研究的小鼠品系中血红蛋白巯基数量的不同。特别是,在DBA、ICRa和ICRb小鼠的血红蛋白中发现了额外的快速反应性巯基,而在C57和ICRc品系中未发现。这些差异也反映在血红蛋白二聚化的敏感性及其与S - 亚硝基半胱氨酸反应的能力上。由于血红蛋白半胱氨酸残基的反应性差异很大,所检测的小鼠品系是研究某些药物的药理和毒理作用的一个有趣但复杂的模型。