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Alkyl Hydroperoxide Reductase as a Determinant of Parasite Antiperoxide Response in Toxoplasma gondii
Oxidative Medicine and Cellular Longevity Pub Date : 2021-09-22 , DOI: 10.1155/2021/1675652
Jinwen Wang 1 , Qianqian Tan 1 , Junpeng Chen 1 , Xiaomei Liu 1 , Zeyan Di 1 , Qianqian Xiao 1 , Jinxuan Li 1 , Xiaomin Zhao 1, 2, 3 , Xiao Zhang 1, 2, 3
Affiliation  

Toxoplasma gondii is a protozoan parasite that is widely parasitic in the nucleated cells of warm-blooded animals. Bioinformatic analysis of alkyl hydroperoxide reductase 1 (AHP1) of T. gondii is a member of the Prxs family and exhibits peroxidase activity. Cys166 was certified to be a key enzyme active site of TgAHP1, indicating that the enzyme follows a cysteine-dependent redox process. TgAHP1 was present in a punctate staining pattern anterior to the T. gondii nucleus. Oxidative stress experiments showed that the ∆Ahp1 strain was more sensitive to tert-butyl hydroperoxide (tBOOH) than hydrogen peroxide (H2O2), indicating that tBOOH may be a sensitive substrate for TgAHP1. Under tBOOH culture conditions, the ∆Ahp1 strain was significantly less invasive, proliferative, and pathogenic in mice. This was mainly due to the induction of tBOOH, which increased the level of reactive oxygen species in the parasites and eventually led to apoptosis. This study shows that TgAHP1 is a peroxisomes protein with cysteine-dependent peroxidase activity and sensitive to tBOOH.

中文翻译:

烷基过氧化氢还原酶作为弓形虫寄生虫抗过氧化物反应的决定因素

刚地弓形虫是一种原生动物寄生虫,广泛寄生于温血动物的有核细胞中。T. gondii的烷基氢过氧化物还原酶 1 (AHP1) 的生物信息学分析是 Prxs 家族的成员,并表现出过氧化物酶活性。Cys 166被证明是 TgAHP1 的关键酶活性位点,表明该酶遵循半胱氨酸依赖性氧化还原过程。TgAHP1 存在于弓形虫核前的点状染色模式中。氧化应激实验表明,ΔAhp1 菌株对叔丁基过氧化氢 (tBOOH) 比过氧化氢 (H 2 O 2),表明 tBOOH 可能是 TgAHP1 的敏感底物。在 tBOOH 培养条件下,ΔAhp1 菌株对小鼠的侵袭性、增殖性和致病性显着降低。这主要是由于 tBOOH 的诱导,它增加了寄生虫中活性氧的水平并最终导致细胞凋亡。该研究表明,TgAHP1 是一种过氧化物酶体蛋白,具有半胱氨酸依赖性过氧化物酶活性并对 tBOOH 敏感。
更新日期:2021-09-22
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