PMID- 29665822
OWN - NLM
STAT- MEDLINE
DCOM- 20180925
LR  - 20211204
IS  - 1756-3305 (Electronic)
IS  - 1756-3305 (Linking)
VI  - 11
IP  - 1
DP  - 2018 Apr 17
TI  - Toxoplasma gondii dense granule protein 15 induces apoptosis in choriocarcinoma 
      JEG-3 cells through endoplasmic reticulum stress.
PG  - 251
LID - 10.1186/s13071-018-2835-3 [doi]
LID - 251
AB  - BACKGROUND: Toxoplasma gondii, a single-celled parasite commonly found in 
      mammals, has been shown to induce trophoblast cell apoptosis and subsequently 
      cause fetal damage and abortion. Although dense granule protein 15 (GRA15) has 
      been identified as a key component in innate immunity to T. gondii infection and 
      its pathogenesis, its role in host cell apoptosis remains unclarified. METHODS: 
      Type II GRA15 (GRA15(II)) cDNA was inserted into a plasmid encoding enhanced 
      green fluorescent protein (pEGFP). Choriocarcinoma JEG-3 cells were transfected 
      with either pEGFP or pEGFP-GRA15(II) and cultured for 24 h. Cell apoptosis and 
      endoplasmic reticulum stress (ERS) responses were assessed. Inhibitors targeting 
      inositol-requiring kinase 1alpha (IRE1alpha; 4mu8C, 100 nM) or c-Jun N-terminal kinase 
      (JNK; SP6000125, 20 muM) were added 12 h after plasmid transfection, followed by 
      testing the effect of GRA15(II) on ERS. RESULTS: When compared to pEGFP, 
      pEGFP-GRA15(II) transfection facilitated cell apoptosis (P < 0.05), increased 
      mRNA expression of caspase-3, caspase-4, 78-kDa glucose-regulated protein 
      (GRP78), C/EBP homologous protein (CHOP) and X-box binding protein-1 (XBP1) (all 
      P < 0.05), and promoted protein expression of cleaved caspase-3, cleaved 
      poly(ADP-ribose) polymerase, Bax, CHOP, GRP78, phospho-JNK, and phospho-IRE1alpha 
      (all P < 0.05). The 4mu8C and SP6000125 decreased apoptosis and protein expression 
      of XBP1s, CHOP, TNF receptor-associated factor 2 (TRAF2), phosphorylated 
      apoptosis signal-regulating kinase 1 (ASK1), cleaved caspase-3, phospho-JNK, and 
      Bax (all P < 0.05) in pEGFP-GRA15(II) transfected cells. CONCLUSIONS: Toxoplasma 
      GRA15(II) induced ERS and subsequently caused apoptosis of choriocarcinoma JEG-3 
      cells.
FAU - Wei, Wei
AU  - Wei W
AD  - Department of Immunology, School of Basic Medicine, Anhui Medical University, 
      Hefei, 230032, China.
FAU - Zhang, Fangfang
AU  - Zhang F
AD  - Department of Pathogen Biology and the Key Laboratory of Microbiology (Anhui), 
      School of Basic Medicine, Anhui Medical University, Hefei, 230032, China.
FAU - Chen, He
AU  - Chen H
AD  - Laboratory of Clinical Diagnostics, the First Hospital of Anhui Medical 
      University, Hefei, 230032, China.
FAU - Tang, Yuanyuan
AU  - Tang Y
AD  - Department of Pathogen Biology and the Key Laboratory of Microbiology (Anhui), 
      School of Basic Medicine, Anhui Medical University, Hefei, 230032, China.
FAU - Xing, Tian
AU  - Xing T
AD  - Key Laboratory of Oral Diseases Research of Anhui Province, Hospital of 
      Stomatology, Anhui Medical University, Hefei, 230032, China.
FAU - Luo, Qingli
AU  - Luo Q
AD  - Department of Pathogen Biology and the Key Laboratory of Microbiology (Anhui), 
      School of Basic Medicine, Anhui Medical University, Hefei, 230032, China.
FAU - Yu, Li
AU  - Yu L
AD  - Department of Pathogen Biology and the Key Laboratory of Microbiology (Anhui), 
      School of Basic Medicine, Anhui Medical University, Hefei, 230032, China.
FAU - Du, Jian
AU  - Du J
AD  - Department of Pathogen Biology and the Key Laboratory of Microbiology (Anhui), 
      School of Basic Medicine, Anhui Medical University, Hefei, 230032, China.
FAU - Shen, Jilong
AU  - Shen J
AD  - Department of Immunology, School of Basic Medicine, Anhui Medical University, 
      Hefei, 230032, China. shenjilong53@126.com.
AD  - Department of Pathogen Biology and the Key Laboratory of Microbiology (Anhui), 
      School of Basic Medicine, Anhui Medical University, Hefei, 230032, China. 
      shenjilong53@126.com.
AD  - Laboratory of Clinical Diagnostics, the First Hospital of Anhui Medical 
      University, Hefei, 230032, China. shenjilong53@126.com.
FAU - Zhang, Linjie
AU  - Zhang L
AD  - Department of Immunology, School of Basic Medicine, Anhui Medical University, 
      Hefei, 230032, China. zlj33@ahmu.edu.cn.
LA  - eng
GR  - 81471983/National Natural Science Foundation of China/International
GR  - 81572022/National Natural Science Foundation of China/International
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180417
PL  - England
TA  - Parasit Vectors
JT  - Parasites & vectors
JID - 101462774
RN  - 0 (Endoplasmic Reticulum Chaperone BiP)
RN  - 0 (HSPA5 protein, human)
RN  - 0 (Protozoan Proteins)
RN  - 0 (Recombinant Proteins)
SB  - IM
MH  - *Apoptosis
MH  - Cell Line, Tumor
MH  - Endoplasmic Reticulum Chaperone BiP
MH  - *Endoplasmic Reticulum Stress
MH  - Gene Expression
MH  - *Host-Pathogen Interactions
MH  - Humans
MH  - Plasmids
MH  - Protozoan Proteins/genetics/*metabolism
MH  - Recombinant Proteins/genetics/metabolism
MH  - Toxoplasma/genetics/*pathogenicity
MH  - Transfection
MH  - Trophoblasts/*physiology
PMC - PMC5904991
OTO - NOTNLM
OT  - Apoptosis
OT  - ERS
OT  - GRA15
OT  - JEG-3 cell
OT  - Toxoplasma gondii
COIS- ETHICS APPROVAL AND CONSENT TO PARTICIPATE: All of the protocols used in the 
      study were approved by the Institutional Review Board of the Institute of 
      Biomedicine at Anhui Medical University, Hefei, Anhui, China (Permit Number 
      AMU26-080610). COMPETING INTERESTS: The authors declare that they have no 
      competing interests.
EDAT- 2018/04/19 06:00
MHDA- 2018/09/27 06:00
PMCR- 2018/04/17
CRDT- 2018/04/19 06:00
PHST- 2018/01/10 00:00 [received]
PHST- 2018/04/06 00:00 [accepted]
PHST- 2018/04/19 06:00 [entrez]
PHST- 2018/04/19 06:00 [pubmed]
PHST- 2018/09/27 06:00 [medline]
PHST- 2018/04/17 00:00 [pmc-release]
AID - 10.1186/s13071-018-2835-3 [pii]
AID - 2835 [pii]
AID - 10.1186/s13071-018-2835-3 [doi]
PST - epublish
SO  - Parasit Vectors. 2018 Apr 17;11(1):251. doi: 10.1186/s13071-018-2835-3.