In vitro effects of gliotoxin, a natural proteasome inhibitor, on the infectivity and proteolytic activity of Toxoplasma gondii.
We examined the in vitro effect of increasing gliotoxin concentrations on the infectivity of Toxoplasma gondii for NIH-3T3 murine fibroblasts and on Toxoplasma chymotrypsin-like activity, which is specific to the proteasome. Parasite penetration of host cells was not modified by a high gliotoxin concentration (1 microM), but replication was markedly decreased (approximately 50% inhibition by 0.5 microM gliotoxin). Gliotoxin reduced the chymotrypsin-like activity of the Toxoplasma proteasome, but five times less potently than in HeLa cells.
Laboratoire "Signalisation cellulaire et Parasites", EA 24-99 INSERM U 529, CHU Cochin, Université Paris V, 27 rue du Faubourg Saint-Jacques, 75014 Paris, France. andre.paugam@cch.ap-hop-paris.fr
André
A
Paugam
Claudine
C
Creuzet
Jean
J
Dupouy-Camet
Paule
P
Roisin
D000818:Animals; D002478:Cells, Cultured; D003049:Coccidiostats / Q000378:metabolism / Q000494:pharmacology*; D003546:Cysteine Endopeptidases; D015853:Cysteine Proteinase Inhibitors / Q000378:metabolism / Q000494:pharmacology*; D005912:Gliotoxin / Q000378:metabolism / Q000494:pharmacology*; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors*; D046988:Proteasome Endopeptidase Complex; D014122:Toxoplasma / Q000187:drug effects* / Q000201:enzymology* / Q000469:parasitology; D014123:Toxoplasmosis / Q000188:drug therapy
D003049:Coccidiostats; D015853:Cysteine Proteinase Inhibitors; D009097:Multienzyme Complexes; D005912:Gliotoxin; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex