title: Toxoplasma gondii invasion and replication within neonate mouse astrocytes and changes in apoptosis related molecules.
abstract: Toxoplasma gondii invades any nucleated cell, but different replication speed and effects on survival/apoptosis processes have been found depending on cell type. There are scarce and controversial results regarding the effect of this parasite on host cell apoptosis within the brain. The invasion and replication of T. gondii RH strain within newborn mouse astrocytes were evaluated in the present work. At 4 hpi>90% cells were infected and harbored one to three parasitophorous vacuoles with one tazchyzoite/vacuole. Cell culture massive destruction started after 24 h of exposure, when the parasite already replicated, with a duplication time of around 5 h. The effect of T. gondii infection on apoptosis was also evaluated by changes in some anti- and pro-apoptotic markers. At early infection times decreased Bcl-2, Survivin and PUMA and increased Noxa expression was found, although Survivin and Noxa mRNA levels reverted towards an anti-apoptotic phenotype after 6 h. Caspases 3/7 activity decreased three hours after infection, although it returned to normal levels thereafter. This enzymatic activity was strongly stimulated by Cisplatin (anti-neoplasic drug) but it was inhibited by previous T. gondii infection. Likewise, parasite invasion prevented PARP-1 fragmentation and cell apoptosis induced by the same drug. In conclusion, astrocytes seem to activate some apoptosis signals shortly after infection, but the parasite takes control of the cell and inhibits programmed death for up to 24 h, until it replicates, egresses and generates cellular destruction.
authors.affiliation: Centro de Investigación sobre Enfermedades Infecciosas, Instituto Nacional de Salud Pública, Av. Universidad no. 655, Colonia Santa María Ahuacatitlán, cerrada Pinos y Caminera, Cuernavaca, Morelos, México CP 62100, Mexico. ccontreras@insp.mx
authors.forename: Carla O
authors.initials: CO
authors.lastname: Contreras-Ochoa
authors.forename: Alfredo
authors.initials: A
authors.lastname: Lagunas-Martínez
authors.forename: Jaime
authors.initials: J
authors.lastname: Belkind-Gerson
authors.forename: José
authors.initials: J
authors.lastname: Díaz-Chávez
authors.forename: Dolores
authors.initials: D
authors.lastname: Correa
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000235:genetics* / Q000378:metabolism; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects / Q000469:parasitology*; D001921:Brain / Q000166:cytology; D020169:Caspases / Q000378:metabolism; D002945:Cisplatin / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation; D019254:Genes, bcl-2 / Q000235:genetics; D005904:Glial Fibrillary Acidic Protein; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D015800:Protozoan Proteins / Q000235:genetics* / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D013047:Specific Pathogen-Free Organisms; D000077022:Survivin; D014122:Toxoplasma / Q000254:growth & development / Q000502:physiology*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; C117749:Birc5 protein, mouse; D005904:Glial Fibrillary Acidic Protein; D051034:Inhibitor of Apoptosis Proteins; D009419:Nerve Tissue Proteins; C488588:PUMA protein, mouse; C408009:Pmaip1 protein, mouse; D019253:Proto-Oncogene Proteins c-bcl-2; D015800:Protozoan Proteins; D012097:Repressor Proteins; D000077022:Survivin; D025521:Tumor Suppressor Proteins; C528900:glial fibrillary astrocytic protein, mouse; C499321:Parp1 protein, mouse; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D020169:Caspases; D002945:Cisplatin