Different metabolizing ability of thiol reactants in human and rat blood - Biochemical and pharmacological implications
Different metabolizing ability of thiol reactants in human and rat blood - Biochemical and pharmacological implications
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DOI：
10.1074/jbc.m005156200
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发表时间：
2001-03-09
影响因子：
4.8
通讯作者：
Di Simplicio, P
中科院分区：
文献类型：
--
作者：
Rossi, R;Milzani, A;Di Simplicio, P
通过分析氧化剂、亲电体和NO供体在大鼠和人红细胞中的作用，研究了蛋白质巯基对这些硫醇反应物代谢的影响，氧化剂引起的硫醇稳态变化在两种模型中有明显不同：过氧化氢或联胺处理后，大鼠红细胞中产生了大量的谷胱甘肽蛋白混合二硫化物，而过氧化氢或联胺处理不能在人红细胞中产生，所有形式的谷胱甘肽(还原的、二硫的、蛋白质混合二硫化物)仅在人红细胞中被甲萘二酮诱导消失。用亲电体处理大鼠红细胞产生的谷胱甘肽-S结合物的程度比人的红细胞低得多；谷胱甘肽在大鼠红细胞中只被最低限度地消耗。NO供体S-亚硝基-半胱氨酸在大鼠红细胞中引起快速的转亚硝化反应，产生高水平的S-亚硝基血红蛋白，而在人红细胞中这一反应可忽略不计。所有药物在大鼠体内的清除速度都比在人红细胞中的清除速度快。与人类Hb不同，大鼠血红蛋白包含三个蛋白质SH基团家族；其中一个位于β125位，与硫醇反应物的代谢直接相关。这被认为会显著影响某些药物的生化、药理和毒理作用。
The effect of oxidants, electrophiles, and NO donors in rat or human erythrocytes was analyzed to investigate the influence of protein sulfhydryl groups on the metabolism of these thiol reactants, Oxidant-evoked alterations in thiolic homeostasis were significantly different in the two models; large amounts of glutathione protein mixed disulfides were produced in rat but not in human erythrocytes by treatment with hydroperoxides or diamide, The disappearance of all forms of glutathione (reduced, disulfide, protein mixed disulfide) was induced by menadione only in human erythrocytes. The treatment of rat red blood cells with electrophiles produced glutathione S-conjugates to a much lower extent than inhuman red blood cells; GSH was only minimally depleted in rat red blood cells. The NO donor S-nitroso-cysteine induced a rapid transnitrosation reaction with hemoglobin in rat erythrocytes producing high levels of S-nitrosohemoglobin; this reaction in human red blood cells was negligible. All drugs were cleared more rapidly in rat than in human erythrocytes. Unlike human Hb, rat hemoglobin contains three families of protein SH groups; one of these located at position beta 125 is directly implicated in the metabolism of thiol reactants. This is thought to influence significantly the biochemical, pharmacological, and toxicological effects of some drugs.