scholarly journals Toxoplasma gondii triggers Gi-dependent PI 3-kinase signaling required for inhibition of host cell apoptosis

2006 ◽  
Vol 119 (10) ◽  
pp. 2119-2126 ◽  
Author(s):  
L. Kim
Keyword(s):  
Toxoplasma Gondii ◽  
Host Cell ◽  
Cell Apoptosis ◽  
Kinase Signaling ◽  
Host Cell Apoptosis

Inhibition of host cell apoptosis by Toxoplasma gondii is accompanied by reduced activation of the caspase cascade and alterations of poly(ADP-ribose) polymerase expression

2001 ◽  
Vol 114 (19) ◽  
pp. 3495-3505
Author(s):  
Stefan Goebel ◽  
Uwe Gross ◽  
Carsten G. K. Lüder
Keyword(s):  
Toxoplasma Gondii ◽  
Cytochrome C ◽  
Host Cell ◽  
Cell Apoptosis ◽  
Mrna Levels ◽  
U937 Cells ◽  
Cytochrome C Release ◽  
Protein Levels ◽  
Host Cell Apoptosis ◽  
Caspase Cascade

The obligate intracellular protozoan parasite Toxoplasma gondii has been shown to protect different cell types from apoptosis induced by a variety of pro-apoptotic treatments. However, the precise cell biological mechanisms of this inhibition remained unknown. As shown in this study, apoptosis in human-derived HL-60 and U937 cells induced by treatment with actinomycin D or TNF-α in combination with cycloheximide, respectively, was indeed dose-dependently downregulated by prior infection with T. gondii, as determined by DNA fragmentation assays. Cleavage of caspase 3 and caspase 9 after treatment with pro-apoptotic stimuli was considerably diminished by T. gondii. Furthermore, release of mitochondrial cytochrome c during apoptosis in HL-60 cells was prevented by intracellular parasites and this was correlated with the absence of DNA strand breaks on the single cell level. Inhibition of cytochrome c release coincided with a twofold upregulation of Mcl-1 protein levels in HL-60 and U937 cells, while Bcl-2 expression did not increase after infection. Parasitic interference with the caspase cascade led to a reduced proteolytic cleavage of the nuclear target molecule protein kinase Cδ. In parallel, poly(ADP-ribose) polymerase protein levels were prominently downregulated by T. gondii, irrespective of whether HL-60 and U937 cells had been treated with pro-apototic stimuli or left untreated. However, poly(ADP-ribose) polymerase mRNA levels remained unchanged after infection as determined by RT-PCR analyses. These observations suggest that T. gondii has evolved different mechanisms that may contribute to downregulation of host cell apoptosis, namely inhibition of cytochrome c release and subsequent caspase activation as well as downregulation of poly(ADP-ribose) polymerase protein levels.

Involvement of PI 3 kinase/Akt-dependent Bad phosphorylation in Toxoplasma gondii-mediated inhibition of host cell apoptosis

2013 ◽  
Vol 133 (4) ◽  
pp. 462-471 ◽  
Author(s):  
Juan-Hua Quan ◽  
Guang-Ho Cha ◽  
Wei Zhou ◽  
Jia-Qi Chu ◽  
Yoshifumi Nishikawa ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
Host Cell ◽  
Cell Apoptosis ◽  
Host Cell Apoptosis

scholarly journals Toxoplasma gondiiROP18 Inhibits Human Glioblastoma Cell Apoptosis through Mitochondrial Pathway by Targeting Host Cell P2X1

2018 ◽  
Author(s):  
Li-Juan Zhou ◽  
Min Chen ◽  
Cheng He ◽  
Jing Xia ◽  
Cynthia Y. He ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
Host Cell ◽  
Immune Cells ◽  
Cell Apoptosis ◽  
Type I ◽  
Glioblastoma Cell ◽  
Human Glioblastoma ◽  
Human Glioblastoma Cell ◽  
Host Cell Apoptosis ◽  
Proapoptotic Protein

ABSTRACTIt is known thatToxoplasma gondiiinfection both initiates and inhibits host cell apoptosis through different proapoptotic signaling cascades, but the parasitic factors involved in these processes remain unclear.T. gondiivirulence factor ROP18 has been reported to regulate host cell apoptosis, but the results of this regulation are few reported and contradictory. In this study, we found that immune or neuro cells infected by any one of theT. gondiistrains (RH-type I, ME49-type II, and VEG-type III) showed a significantly lower apoptosis index than their uninfected controls when apoptosis was induced by staurosporine (STS). We further found that ROP18 of RH strain inhibited ATP induced apoptosis in human glioblastoma cells (SF268) with endogenous expression of human proapoptotic protein purinergic receptor 1 (P2X1), but had no effects on the immune cells of RAW264.7 and THP-1 without detectable P2X1 expression, which may indicate that ROP18’s inhibition of host cell apoptosis is related to P2X1. Interestingly, we further identified that ROP18 (RH strain) interacted with P2X1, and over-expression of ROP18 in COS-7 cells inhibited the cell apoptosis mediated by P2X1. We also found that ROP18 of RH strain inhibited P2X1-mediated Ca2+influx, translocation of cytochrome C from mitochondria to cytoplasm, and 1 ATP-triggered caspases activation. Collectively, these findings supported that ROP18 inhibited the host cell apoptosis through the intrinsic mitochondria pathway by targeting host cell P2X1, thereby suggesting a sensor role of the host proapoptotic protein P2X1 in this processAuthor summaryThe obligate intracellular protozoanToxoplasma gondiihas been shown to modulate cell apoptosis through different apoptotic pathways. However, the consequences are various and even contradictory, and the parasite effectors and the precise biological mechanisms remain unclear. Herein we showed thatT. gondiiof type I, II, and III strains could inhibit the apoptosis of neuro cells and immune cells.Toxoplasma gondiiROP18 (RH strain) inhibited apoptosis of human glioblastoma cell SF268 by targeting C terminal of host cell P2X1 protein, but not through proteasome-dependent degradation of P2X1.

Characterization of a cysteine protease from Tritrichomonas foetus that induces host-cell apoptosis

2008 ◽  
Vol 477 (2) ◽  
pp. 239-243 ◽  
Author(s):  
John J. Lucas ◽  
Gary R. Hayes ◽  
Hardip K. Kalsi ◽  
Robert O. Gilbert ◽  
Yongchool Choe ◽  
...  
Keyword(s):  
Host Cell ◽  
Cysteine Protease ◽  
Cell Apoptosis ◽  
Tritrichomonas Foetus ◽  
Host Cell Apoptosis
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