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克氏锥虫中依赖于三巯基丙胺的过氧化物酶系统的证据。

Evidence for a trypanothione-dependent peroxidase system in Trypanosoma cruzi.

作者信息

Lopez J A, Carvalho T U, de Souza W, Flohé L, Guerrero S A, Montemartini M, Kalisz H M, Nogoceke E, Singh M, Alves M J, Colli W

机构信息

Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo, Brazil.

出版信息

Free Radic Biol Med. 2000 Mar 1;28(5):767-72. doi: 10.1016/s0891-5849(00)00159-3.

Abstract

Hydroperoxide metabolism in Crithidia fasciculata has recently been shown to be catalyzed by a cascade of three oxidoreductases comprising trypanothione reductase (TR), tryparedoxin (TXN1), and tryparedoxin peroxidase (TXNPx) (Nogoceke et al., Biol. Chem. 378, 827-836, 1997). The existence of this metabolic system in the human pathogen Trypanosoma cruzi is supported here by immunohistochemistry. Epimastigotes of T. cruzi display strong immunoreactivity with antibodies raised against TXN1 and TXNPx of C. fasciculata. In addition, a full-length open reading frame presumed to encode a peroxiredoxin-type protein in T. cruzi (Acc. Nr. AJ 012101) was heterologously expressed in Escherichia coli and shown to exhibit tryparedoxin peroxidase activity. With TXN, TXNPx, trypanothione and TR, T. cruzi possesses all components constituting the crithidial peroxidase system. It is concluded that the antioxidant defense of T. cruzi also depends on the NADPH-fuelled, trypanothione-mediated enzymatic hydroperoxide metabolism.

摘要

近来研究表明,克氏锥虫中的过氧化氢代谢由三种氧化还原酶组成的级联反应催化,这三种酶包括锥虫硫醇还原酶(TR)、锥虫硫氧还蛋白(TXN1)和锥虫硫氧还蛋白过氧化物酶(TXNPx)(Nogoceke等人,《生物化学》378卷,827 - 836页,1997年)。本文通过免疫组织化学方法证实了人类病原体克氏锥虫中存在这种代谢系统。克氏锥虫的无鞭毛体与针对克氏锥虫TXN1和TXNPx产生的抗体呈现出强烈的免疫反应性。此外,一个推测在克氏锥虫中编码过氧化物还原酶型蛋白的全长开放阅读框(登录号AJ 012101)在大肠杆菌中进行了异源表达,并显示出具有锥虫硫氧还蛋白过氧化物酶活性。克氏锥虫拥有TXN、TXNPx、锥虫硫醇和TR,具备构成克氏锥虫过氧化物酶系统的所有成分。由此得出结论,克氏锥虫的抗氧化防御也依赖于由NADPH供能、锥虫硫醇介导的酶促过氧化氢代谢。

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