Alkyl Hydroperoxide Reductase as a Determinant of Parasite Antiperoxide Response in Toxoplasma gondii.

Alkyl Hydroperoxide Reductase as a Determinant of Parasite Antiperoxide Response in Toxoplasma gondii.
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烷基氢过氧化物还原酶作为弓形虫寄生虫抗过氧化物反应的决定因素

DOI:
10.1155/2021/1675652
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发表时间:
2021
影响因子:
--
通讯作者:
Zhang X
Zhang X
中科院分区:
生物学2区
文献类型:
--
作者:
Wang J;Tan Q;Chen J;Liu X;Di Z;Xiao Q;Li J;Zhao X;Zhang X

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弓形虫是一种原生动物寄生虫,广泛寄生在温血动物的有核细胞中。弓形虫烷基过氧化氢还原酶1(AHP1)的生物信息学分析是Prxs家族的成员,具有过氧化物酶活性。Cys166被证明是TgAHP1的关键酶活性部位,表明该酶遵循半胱氨酸依赖的氧化还原过程。TgAHP1在弓形虫细胞核前呈点状染色。氧化应激实验表明,∆Ahp1菌株对叔丁基氢过氧化氢(TBOOH)的敏感性高于过氧化氢(H_2O_2),表明tBOOH可能是TgAHP1的敏感底物。在tBOOH培养条件下,∆Ahp1株在小鼠中的侵袭性、增殖性和致病性显著较低。这主要是由于tBOOH的诱导,它增加了寄生虫中的活性氧物种的水平,最终导致了细胞凋亡。本研究表明,TgAHP1是一种具有半胱氨酸依赖的过氧化物酶活性的过氧体蛋白,对tBOOH敏感。
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.
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