title: Direct inhibition of cytochrome c-induced caspase activation in vitro by Toxoplasma gondii reveals novel mechanisms of interference with host cell apoptosis.
abstract: The intracellular parasite Toxoplasma gondii is known to inhibit apoptosis of its host cell. The molecular mechanisms of this interference are, however, not yet completely understood. We show here that viable parasites prominently inhibited the activation of caspase 3/7 induced by cytochrome c, dATP and dithiothreitol in cytosolic extracts of human-derived Jurkat leukemic T cells. In contrast, granzyme B-induced caspase activity was only slightly diminished. De novo protein biosynthesis by T. gondii was dispensable for the inhibition of cytochrome c-induced caspase activation. Furthermore, a complete parasite lysate or, more importantly, molecules released by extracellular parasites mediated the interaction with the caspase cascade. The cell-free system applied here is thus a valuable tool to study the interaction of T. gondii and possibly other intracellular pathogens with host cell apoptosis.
authors.affiliation: Institut für Medizinische Mikrobiologie, Georg-August-Universität, Göttingen, Germany.
authors.forename: Philine
authors.initials: P
authors.lastname: Keller
authors.forename: Frieder
authors.initials: F
authors.lastname: Schaumburg
authors.forename: Silke F
authors.initials: SF
authors.lastname: Fischer
authors.forename: Georg
authors.initials: G
authors.lastname: Häcker
authors.forename: Uwe
authors.initials: U
authors.lastname: Gross
authors.forename: Carsten G K
authors.initials: CG
authors.lastname: Lüder
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D053148:Caspase 3; D053179:Caspase 7; D061945:Caspase Inhibitors; D018929:Cell Culture Techniques; D045304:Cytochromes c / Q000037:antagonists & inhibitors*; D006801:Humans; D019169:Jurkat Cells; D014122:Toxoplasma / Q000166:cytology / Q000472:pathogenicity*
chemical_list: D061945:Caspase Inhibitors; D045304:Cytochromes c; C505407:CASP3 protein, human; C505520:CASP7 protein, human; D053148:Caspase 3; D053179:Caspase 7