T-gondii rhoptry protein ROP18 induces apoptosis of neural cells via endoplasmic reticulum stress pathway

被引:23
作者
Wan, Lijuan [1 ]
Gong, Lingli [1 ]
Wang, Wei [2 ]
An, Ran [1 ]
Zheng, Meijuan [3 ]
Jiang, Zongru [1 ]
Tang, Yuewen [1 ]
Zhang, Yihua [2 ,4 ]
Chen, He [3 ,4 ]
Yu, Li [4 ,5 ]
Shen, Jilong [2 ,4 ]
Du, Jian [1 ,4 ]
机构
[1] Anhui Med Univ, Sch Basic Med Sci, Dept Biochem & Mol Biol, Hefei 230032, Peoples R China
[2] Anhui Med Univ, Sch Basic Med Sci, Dept Parasitol, Hefei 230032, Peoples R China
[3] Anhui Med Univ, Affiliated Hosp 1, Clin Lab, Hefei 230032, Anhui, Peoples R China
[4] Key Lab Zoonoses & Pathogen Biol Anhui, Hefei, Peoples R China
[5] Anhui Med Univ, Dept Microbiol, Hefei 230032, Peoples R China
来源
PARASITES & VECTORS | 2015年 / 8卷
基金
中国国家自然科学基金;
关键词
T; gondii; ROP18; ER stress; Apoptosis; STEM-CELLS; VIRULENCE; IMMUNOPATHOGENESIS; INFECTION; BRAIN; DEATH; MICE;
D O I
10.1186/s13071-015-1103-z
中图分类号
R38 [医学寄生虫学]; Q [生物科学];
学科分类号
07 ; 0710 ; 09 ; 100103 ;
摘要
Background: The neurotropic parasite T. gondii is widespread among mammalian hosts including humans. During the course of T. gondii infection, the central nervous system is the most commonly damaged of all invasive organs. The polymorphic rhoptry protein ROP18 has been identified as a key factor in the pathogenesis of T. gondii; however, the molecular mechanism by which this protein exerts neuropathogenesis remains elusive. Methods: Immunofluorescence staining was performed to detect neuropathogenesis of the mouse brain tissues. The apoptosis of neural cells and the expressions of related proteins in the endoplasmic reticulum stress (ER Stress)-mediated apoptosis pathway were detected by flow cytometry and Western blotting. Results: Immunofluorescence staining reveals induction of the propidium iodide (PI) - positive neural cells in mouse cerebral cortex and hippocampus infected with ROP18 over-expressing transgenic tachyzoites. Western blotting analyses reveal that ROP18 increases the expressions of cleaved caspase-12, CHOP and cleaved caspase-3 when compared to the control groups. After the pretreatment of Z-ATAD-FMK (a specific caspase-12 inhibitor), the apoptotic level of neural cells had an apparent decline, and correspondingly, the expressions of those related proteins were notably decreased. Conclusions: Our findings here highlight that the virulence factor ROP18 in T. gondii may contribute to neuronal apoptosis through the ER stress-mediated apoptosis pathway, which may be a potential molecular mechanism responsible for neurological disorders of toxoplasmosis.
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页数:9
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