T. gondii rhoptry protein ROP18 induces apoptosis of neural cells via endoplasmic reticulum stress pathway.
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.
Distinguished Young Scholar of Anhui Province. Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Anhui Medical University, No.81 Meishan Road, Anhui, P.O. Box 71, Hefei, 230032, China. 306776470@qq.com.
Lijuan
L
Wan
Distinguished Young Scholar of Anhui Province. Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Anhui Medical University, No.81 Meishan Road, Anhui, P.O. Box 71, Hefei, 230032, China. 1096267547@qq.com.
Lingli
L
Gong
Department of Parasitology, School of Basic Medical Sciences, Anhui Medical University, Hefei, China. 187028180@qq.com.
Wei
W
Wang
Distinguished Young Scholar of Anhui Province. Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Anhui Medical University, No.81 Meishan Road, Anhui, P.O. Box 71, Hefei, 230032, China. enron90721@163.com.
Ran
R
An
Clinical Laboratory, the First Affiliated Hospital, Anhui Medical University, Hefei, Anhui, China. 601449005@qq.com.
Meijuan
M
Zheng
Distinguished Young Scholar of Anhui Province. Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Anhui Medical University, No.81 Meishan Road, Anhui, P.O. Box 71, Hefei, 230032, China. 1804919386@qq.com.
Zongru
Z
Jiang
Distinguished Young Scholar of Anhui Province. Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Anhui Medical University, No.81 Meishan Road, Anhui, P.O. Box 71, Hefei, 230032, China. 1731625930@qq.com.
Yuewen
Y
Tang
Department of Parasitology, School of Basic Medical Sciences, Anhui Medical University, Hefei, China. 948535532@qq.com.|The Key Laboratory of Zoonoses and Pathogen Biology Anhui, Hefei, China. 948535532@qq.com.
Yihua
Y
Zhang
Clinical Laboratory, the First Affiliated Hospital, Anhui Medical University, Hefei, Anhui, China. 291534933@qq.com.|The Key Laboratory of Zoonoses and Pathogen Biology Anhui, Hefei, China. 291534933@qq.com.
He
H
Chen
The Key Laboratory of Zoonoses and Pathogen Biology Anhui, Hefei, China. 840693120@qq.com.|Department of Microbiology, Anhui Medical University, Hefei, China. 840693120@qq.com.
Li
L
Yu
Department of Parasitology, School of Basic Medical Sciences, Anhui Medical University, Hefei, China. shenjilong53@126.com.|The Key Laboratory of Zoonoses and Pathogen Biology Anhui, Hefei, China. shenjilong53@126.com.
Jilong
J
Shen
Distinguished Young Scholar of Anhui Province. Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Anhui Medical University, No.81 Meishan Road, Anhui, P.O. Box 71, Hefei, 230032, China. dujane@163.com.|The Key Laboratory of Zoonoses and Pathogen Biology Anhui, Hefei, China. dujane@163.com.
Jian
J
Du
D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D001921:Brain / Q000473:pathology; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D005434:Flow Cytometry; D054884:Host-Pathogen Interactions; D051379:Mice; D009474:Neurons / Q000469:parasitology* / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D015800:Protozoan Proteins; D014122:Toxoplasma / Q000502:physiology*; D014124:Toxoplasmosis, Animal / Q000469:parasitology / Q000473:pathology
D015800:Protozoan Proteins; D017346:Protein Serine-Threonine Kinases; C556793:ROP18 protein, Toxoplasma gondii