Programmed Cell Death 5 from Toxoplasma gondii: a secreted molecule that exerts a pro-apoptotic effect on host cells.
Although parasite-infected host cells become resistant to apoptosis, uninfected bystander cells undergo apoptosis during Toxoplasma gondii infection. The Programmed Cell Death 5 (TgPDCD5) gene, a homologue of the human apoptosis-related molecule, was cloned from a T. gondii full-length cDNA database and subsequently characterized. The native TgPDCD5 was located in the cytosol and also detected in the secreted fraction. Immuno-electron microscopic analysis showed TgPDCD5 was primarily located close to the rhoptries or vesicle-like structures near the surface membrane of the parasite. Studies using recombinant TgPDCD5 (rTgPDCD5) demonstrated that host cells internalize the molecule in a heparan sulfate proteoglycan-binding motif-dependent manner. Furthermore, the addition of rTgPDCD5 to culture medium resulted in the enhancement of host-cell apoptosis triggered by etoposide in macrophage cell line J774A.1 and leukemic cell line HL-60 cells. Additionally, rTgPDCD5 induced apoptosis in J774A.1 cells in the presence of IFN-gamma. This report is the first to identify a parasitic molecule of T. gondii that has a pro-apoptotic effect on host cells.
Bannai
Hiroshi
H
National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Hokkaido, Japan.
Nishikawa
Yoshifumi
Y
Matsuo
Tomohide
T
Kawase
Osamu
O
Watanabe
Junichi
J
Sugimoto
Chihiro
C
Xuan
Xuenan
X
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000302:isolation & purification* / Q000378:metabolism*; D002460:Cell Line; D003001:Cloning, Molecular; D006224:Cricetinae; D003593:Cytoplasm / Q000737:chemistry; D018076:DNA, Complementary / Q000235:genetics; D016054:DNA, Protozoan / Q000235:genetics; D005260:Female; D006801:Humans; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D016253:Microscopy, Immunoelectron; D008969:Molecular Sequence Data; D015388:Organelles / Q000737:chemistry / Q000648:ultrastructure; D015800:Protozoan Proteins / Q000235:genetics / Q000302:isolation & purification* / Q000378:metabolism*; D016415:Sequence Alignment; D014122:Toxoplasma / Q000737:chemistry* / Q000235:genetics
D051017:Apoptosis Regulatory Proteins; D018076:DNA, Complementary; D016054:DNA, Protozoan; D015800:Protozoan Proteins