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多胺作为克氏锥虫中对抗脂质过氧化的一种防御机制。

Polyamines as a defense mechanism against lipoperoxidation in Trypanosoma cruzi.

作者信息

Hernández Susana M, Sánchez Marcela S, de Tarlovsky Martha N Schwarcz

机构信息

School of Medicine, Universidad Abierta Interamericana (UAI), Buenos Aires, Argentina.

出版信息

Acta Trop. 2006 Apr;98(1):94-102. doi: 10.1016/j.actatropica.2006.02.005. Epub 2006 Mar 30.

Abstract

The polyamines, spermine and spermidine--organic polycations that are absolutely required for eukaryotic cell growth--are shown here to function in Trypanosoma cruzi epimastigotes, as protectors of membrane lipoperoxidation by reactive oxygen species generated either by H2O2/Fe2+ or nifurtimox. In vitro, spermine and spermidine inhibited lipoperoxidation in a dose dependent manner. Spermine was more efficient than spermidine in its inhibitory effect. Lipid peroxidation induced by H2O2 showed an IC50 of 0.55 mM for spermine and 0.9 mM for spermidine while an IC50 of 0.8 mM for spermine and 1.5 mM for spermidine were observed when lipoperoxidation was elicited by nifurtimox. Likewise in vivo, both exogenously added spermine and spermidine or endogenous increase of spermine levels induced by phorbol ester, protected against lipoperoxidation and decreased citotoxicity provoked by nifurtimox. Putrescine and cadaverine, also present in T. cruzi had no effect at all. None of the polyamines had any effect neither on the scavenging of superoxide anion nor on the regulation of antioxidant enzymes such as superoxide dismutase and peroxidases involved in H2O2 detoxification. Here we point out that spermine, by acting as a protector of membrane lipoperoxidation might contribute to survival of T. cruzi continuously exposed to oxidative stress.

摘要

多胺、精胺和亚精胺——真核细胞生长绝对必需的有机聚阳离子——在本文中显示在克氏锥虫的上鞭毛体中发挥作用,作为由H2O2/Fe2+或硝呋替莫产生的活性氧对膜脂质过氧化的保护剂。在体外,精胺和亚精胺以剂量依赖的方式抑制脂质过氧化。精胺的抑制作用比亚精胺更有效。H2O2诱导的脂质过氧化对精胺的IC50为0.55 mM,对亚精胺为0.9 mM,而当由硝呋替莫引发脂质过氧化时,精胺的IC50为0.8 mM,亚精胺为1.5 mM。同样在体内,外源性添加的精胺和亚精胺或佛波酯诱导的精胺水平内源性增加,都能防止脂质过氧化并降低硝呋替莫引起的细胞毒性。克氏锥虫中也存在的腐胺和尸胺则完全没有作用。这些多胺对超氧阴离子的清除或对参与H2O2解毒的抗氧化酶如超氧化物歧化酶和过氧化物酶的调节均无任何影响。在此我们指出,精胺作为膜脂质过氧化的保护剂,可能有助于持续暴露于氧化应激的克氏锥虫的存活。

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