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Thiol regulation by Mn porphyrins, commonly known as SOD mimics.
Redox Biology ( IF 10.7 ) Pub Date : 2019-02-13 , DOI: 10.1016/j.redox.2019.101139
Ines Batinic-Haberle 1 , Margaret E Tome 2
Affiliation  

Superoxide dismutases play an important role in human health and disease. Three decades of effort have gone into synthesizing SOD mimics for clinical use. The result is the Mn porphyrins which have SOD-like activity. Several clinical trials are underway to test the efficacy of these compounds in patients, particularly as radioprotectors of normal tissue during cancer treatment. However, aqueous chemistry data indicate that the Mn porphyrins react equally well with multiple redox active species in cells including H2O2, O2•-, ONOO-, thiols, and ascorbate among others. The redox potential of the Mn porphyrins is midway between the potentials for the oxidation and reduction of O2•-. This positions them to react equally well as oxidants and reductants in cells. The result of this unique chemistry is that: 1) the species the Mn porphyrins react with in vivo will depend on the relative concentrations of the reactive species and Mn porphyrins in the cell of interest, and 2) the Mn porphyrins will act as catalytic (redox cycling) agents in vivo. The ability of the Mn porphyrins to catalyze protein S-glutathionylation means that Mn porphyrins have the potential to globally modulate cellular redox regulatory signaling networks. The purpose of this review is to summarize the data that indicate the Mn porphyrins have diverse reactions in vivo that are the basis of the observed biological effects. The ability to catalyze multiple reactions in vivo expands the potential therapeutic use of the Mn porphyrins to disease models that are not SOD based.



中文翻译:

锰卟啉(通常称为 SOD 模拟物)对硫醇的调节。

超氧化物歧化酶在人类健康和疾病中发挥着重要作用。三十年的努力致力于合成用于临床的 SOD 模拟物。结果是具有类 SOD 活性的锰卟啉。多项临床试验正在进行中,以测试这些化合物对患者的功效,特别是在癌症治疗期间作为正常组织的辐射保护剂。然而,水化学数据表明,锰卟啉与细胞中的多种氧化还原活性物质反应同样良好,包括H 2 O 2、O 2 •-、ONOO -、硫醇和抗坏血酸等。锰卟啉的氧化还原电势介于O 2 ·-的氧化电势和还原电势之间。这使得它们能够与细胞中的氧化剂和还原剂发生同样的反应。这种独特的化学反应的结果是:1) 锰卟啉在体内反应的物种将取决于感兴趣细胞中活性物种和锰卟啉的相对浓度,2) 锰卟啉将充当催化剂(体内氧化还原循环)剂。锰卟啉催化蛋白质 S-谷胱甘肽化的能力意味着锰卟啉具有全局调节细胞氧化还原调节信号网络的潜力。本综述的目的是总结表明锰卟啉在体内具有多种反应的数据,这是观察到的生物效应的基础。体内催化多种反应的能力将锰卟啉的潜在治疗用途扩展到非 SOD 疾病模型。

更新日期:2019-02-13
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