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Toxoplasma gondii induce apoptosis of neural stem cells via endoplasmic reticulum stress pathway

Published online by Cambridge University Press:  10 March 2014

TENG WANG ,
JIE ZHOU ,
XIAOFENG GAN ,
HUA WANG ,
XIAOJUAN DING ,
LINGZHI CHEN ,
YONGZHONG WANG ,
JIAN DU ,
JILONG SHEN  and
LI YU
TENG WANG
Affiliation:
Department of Microbiology and Parasitology, Anhui Provincial Laboratory of Microbiology and Parasitology, Anhui Key Laboratory of Zoonoses, Anhui Medical University, Hefei 230032, PR China
JIE ZHOU
Affiliation:
Department of Microbiology and Parasitology, Anhui Provincial Laboratory of Microbiology and Parasitology, Anhui Key Laboratory of Zoonoses, Anhui Medical University, Hefei 230032, PR China
XIAOFENG GAN
Affiliation:
Department of Microbiology and Parasitology, Anhui Provincial Laboratory of Microbiology and Parasitology, Anhui Key Laboratory of Zoonoses, Anhui Medical University, Hefei 230032, PR China
HUA WANG
Affiliation:
Department of Microbiology and Parasitology, Anhui Provincial Laboratory of Microbiology and Parasitology, Anhui Key Laboratory of Zoonoses, Anhui Medical University, Hefei 230032, PR China Department of Neural Endocrinology, Feidong People's Hospital, Hefei 231600, PR China
XIAOJUAN DING
Affiliation:
Department of Microbiology and Parasitology, Anhui Provincial Laboratory of Microbiology and Parasitology, Anhui Key Laboratory of Zoonoses, Anhui Medical University, Hefei 230032, PR China
LINGZHI CHEN
Affiliation:
Department of Microbiology and Parasitology, Anhui Provincial Laboratory of Microbiology and Parasitology, Anhui Key Laboratory of Zoonoses, Anhui Medical University, Hefei 230032, PR China
YONGZHONG WANG
Affiliation:
School of Life Sciences, Anhui University, Hefei 230039, PR China Department of Biomedical Engineering, Ohio State University, Columbus, OH 43210, USA
JIAN DU
Affiliation:
Department of Biochemistry, Anhui Medical University, Hefei 230032, PR China
JILONG SHEN
Affiliation:
Department of Microbiology and Parasitology, Anhui Provincial Laboratory of Microbiology and Parasitology, Anhui Key Laboratory of Zoonoses, Anhui Medical University, Hefei 230032, PR China
LI YU*
Affiliation:
Department of Microbiology and Parasitology, Anhui Provincial Laboratory of Microbiology and Parasitology, Anhui Key Laboratory of Zoonoses, Anhui Medical University, Hefei 230032, PR China
*
* Corresponding author: Department of Microbiology and Parasitology, Anhui Medical University, Hefei 230032, China. E-mail: [email protected]
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Summary

Toxoplasma gondii is a major cause of congenital brain disease; however, the underlying mechanism of neuropathogenesis in brain toxoplasmosis remains elusive. To explore the role of T. gondii in the development of neural stem cells (NSCs), NSCs were isolated from GD14 embryos of ICR mice and were co-cultured with tachyzoites of T. gondii RH strain. We found that apoptosis levels of the NSCs co-cultured with 1×106 RH tachyzoites for 24 and 48 h significantly increased in a dose-dependent manner, as compared with the control. Western blotting analysis displayed that the protein level of C/EBP homologous protein (CHOP) was up-regulated, and caspase-12 and c-Jun N-terminal kinase (JNK) were activated in the NSCs co-cultured with the parasites. Pretreatment with endoplasmic reticulum stress (ERS) inhibitor (TUDCA) and caspase-12 inhibitor (Z-ATAD-FMK) inhibited the expression or activation of the key molecules involved in the ERS-mediated apoptotic pathway, and subsequently decreased the apoptosis levels of the NSCs induced by the T. gondii. The findings here highlight that T. gondii induced apoptosis of the NSCs through the ERS signal pathway via activation of CHOP, caspase-12 and JNK, which may constitute a potential molecular mechanism responsible for the cognitive disturbance in neurological disorders of T. gondii.

Keywords

Toxoplasma gondiineural stem cellsendoplasmic reticulum stressapoptosis
Type
Research Article
Information
Parasitology , Volume 141 , Issue 7 , June 2014 , pp. 988 - 995
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Copyright
Copyright © Cambridge University Press 2014 

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