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Parasit Vectors. 2015 Feb 4;8:73. doi: 10.1186/s13071-015-0670-3.

Toxoplasma gondii prevalent in China induce weaker apoptosis of neural stem cells C17.2 via endoplasmic reticulum stress (ERS) signaling pathways.

Zhou J1,2, Gan X3, Wang Y4,5, Zhang X6, Ding X7, Chen L8, Du J9, Luo Q10, Wang T11,12, Shen J13, Yu L14.

Author information

1
Department of Microbiology and Parasitology, Anhui Provincial Laboratory of Microbiology and Parasitology, Anhui Key Laboratory of Zoonoses, Anhui Medical University, Hefei, 230032, PR China. 402822189@qq.com.
2
Clinical Laboratory, People's Hospital of Huaibei, Huaibei, 235000, PR China. 402822189@qq.com.
3
Department of Microbiology and Parasitology, Anhui Provincial Laboratory of Microbiology and Parasitology, Anhui Key Laboratory of Zoonoses, Anhui Medical University, Hefei, 230032, PR China. 814819028@qq.com.
4
College of Life Sciences, Zhejiang Sci-Tech University, Hangzhou, 310018, PR China. yongzhong00@126.com.
5
School of Life Sciences, Anhui University, Hefei, 230039, PR China. yongzhong00@126.com.
6
Department of Microbiology and Parasitology, Anhui Provincial Laboratory of Microbiology and Parasitology, Anhui Key Laboratory of Zoonoses, Anhui Medical University, Hefei, 230032, PR China. 493523189@qq.com.
7
Department of Microbiology and Parasitology, Anhui Provincial Laboratory of Microbiology and Parasitology, Anhui Key Laboratory of Zoonoses, Anhui Medical University, Hefei, 230032, PR China. 1344539489@qq.com.
8
Department of Microbiology and Parasitology, Anhui Provincial Laboratory of Microbiology and Parasitology, Anhui Key Laboratory of Zoonoses, Anhui Medical University, Hefei, 230032, PR China. 1098728120@qq.com.
9
Department of Biochemistry, Anhui Medical University, Hefei, 230032, PR China. 2387859015@qq.com.
10
Department of Microbiology and Parasitology, Anhui Provincial Laboratory of Microbiology and Parasitology, Anhui Key Laboratory of Zoonoses, Anhui Medical University, Hefei, 230032, PR China. 345052511@qq.com.
11
Department of Microbiology and Parasitology, Anhui Provincial Laboratory of Microbiology and Parasitology, Anhui Key Laboratory of Zoonoses, Anhui Medical University, Hefei, 230032, PR China. 878830640@qq.com.
12
HTS & Compound Management, HD Biosciences Corporation, Shanghai, 201201, PR China. 878830640@qq.com.
13
Department of Microbiology and Parasitology, Anhui Provincial Laboratory of Microbiology and Parasitology, Anhui Key Laboratory of Zoonoses, Anhui Medical University, Hefei, 230032, PR China. shenjilong53@126.com.
14
Department of Microbiology and Parasitology, Anhui Provincial Laboratory of Microbiology and Parasitology, Anhui Key Laboratory of Zoonoses, Anhui Medical University, Hefei, 230032, PR China. lilyyu33@126.com.

Abstract

BACKGROUND:

Toxoplasma gondii, an obligate intracellular pathogen, has a strong affinity for the nervous system. TgCtwh3, a representative Chinese 1 Toxoplasma strain prevalent in China, has the polymorphic features of the effectors ROP16I/III with type I and GRA15II with type II Toxoplasma strains. The interaction of this atypical strain with host cells remains extremely elusive.

METHODS:

Using a transwell system, neural stem cells C17.2 were co-cultured with the tachyzoites of TgCtwh3 or standard type I RH strain. The apoptosis levels of C17.2 cells and the expression levels of related proteins in the endoplasmic reticulum stress (ERS)-mediated pathway were detected by flow cytometry and Western blotting.

RESULTS:

The apoptosis level of C17.2 cells co-cultured with TgCtwh3 had a significant increase compared to the negative control group; however, the apoptosis level in the TgCtwh3 group was significantly lower than that in the RH co-culture group. Western blotting analyses reveal that, after the C17.2 cells were co-cultured with TgCtwh3 and RH tachyzoites, the expression levels of caspase-12, CHOP and p-JNK in the cells increased significantly when compared to the control groups. After the pretreatment of Z-ATAD-FMK, an inhibitor of caspase-12, the apoptosis level of the C17.2 cells co-cultured with TgCtwh3 or RH tachyzoites had an apparent decline, and correspondingly, the expression levels of those related proteins were notably decreased.

CONCLUSIONS:

Our findings suggest that TgCtwh3 may induce the apoptosis of the C17.2 cells by up-regulation of caspase-12, CHOP, and p-JNK, which are associated with ERS signaling pathways. This work contributes to better understanding the possible mechanism of brain pathology induced by T. gondii Chinese 1 isolates prevalent in China, and also reveals the potential value of ERS inhibitors to treat such related diseases in the future.

PMID:
25649541
PMCID:
PMC4322664
DOI:
10.1186/s13071-015-0670-3
[Indexed for MEDLINE]
Free PMC Article

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