The antioxidant systems in Toxoplasma gondii and the role of cytosolic catalase in defence against oxidative injury

被引:103
作者
Kwok, LY
Schlüter, D
Clayton, C
Soldati, D
机构
[1] Univ London Imperial Coll Sci Technol & Med, Dept Biol Sci, London SW7 2AZ, England
[2] Heidelberg Univ, Univ Klinikum Mannheim, Inst Med Mikrobiol & Hyg, D-68167 Mannheim, Germany
[3] Heidelberg Univ, Zentrum Mol Biol, D-69120 Heidelberg, Germany
关键词
D O I
10.1046/j.1365-2958.2003.03823.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Superoxide dismutase, catalase, glutathione peroxidase and peroxiredoxins form an antioxidant network protecting cells against reactive oxygen species (ROS). Catalase is a potent H2O2-detoxifying enzyme, which is unexpectedly absent in some members of the Kinetoplastida and Apicomplexa, but present in Toxoplasma gondii. In T. gondii, catalase appears to be cytosolic. In addition, T. gondii also possesses genes coding for other types of peroxidases, including glutathione/thioredoxin-like peroxidases and peroxiredoxins. This study presents a detailed analysis of the role of catalase in the parasite and reports the existence of antioxidant enzymes localized in the cytosol and the mitochondrion of T. gondii. The catalase gene was disrupted and, in addition, T. gondii cell lines overexpressing either catalase or a cytosolic 1-cys peroxiredoxin, TgPrx2, under the control of a strong promoter were created. Analysis of these mutants confirmed that the catalase activity is cytosolic and is encoded by a unique gene in T. gondii. Furthermore, the catalase confers protection against H2O2 exposure and contributes to virulence in mice. The overexpression of Prx2 also increases protection against H2O2 treatment, suggesting that catalase and other peroxidases function as a defence mechanism against endogenously produced reactive oxygen intermediates and the oxidative stress imposed by the host.
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页码:47 / 61
页数:15
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