Effects of buthionine sulfoximine nifurtimox and benznidazole upon trypanothione and metallothionein proteins in Trypanosoma cruzi.
Proteins rich in sulfhydryl groups, such as metallothionein, are present in several strains of the parasite Trypanosoma cruzi, the etiological agent of Chagas' disease. Metallothionein-like protein concentrations ranged from 5.1 to 13.2 pmol/mg protein depending on the parasite strain and growth phase. Nifurtimox and benznidazole, used in the treatment of Chagas' disease, decreased metallothionein activity by approximately 70%. T. cruzi metallothionein was induced by ZnCl2. Metallothionein from T. cruzi was partially purified and its monobromobimane derivative showed a molecular weight of approximately 10,000 Da by SDS-PAGE analysis. The concentration of trypanothione, the major glutathione conjugate in T. cruzi, ranged from 3.8 to 10.8 nmol/mg protein, depending on the culture phase. The addition of buthionine sulfoximine to the protozoal culture considerably reduced the concentration of trypanothione and had no effect upon the metallothionein concentration. The possible contribution of metallothionein-like proteins to drug resistance in T. cruzi is discussed.
Maya
Juan Diego
JD
Faculty of Medicine, ICBM, Program of Molecular and Clinical Pharmacology, University of Chile, Casilla 70000, Santiago 7, Chile. jmaya@med.uchile.cl
Rodríguez
Andrés
A
Pino
Laura
L
Pabón
Adriana
A
Ferreira
Jorge
J
Pavani
Mario
M
Repetto
Yolanda
Y
Morello
Antonio
A
D000818:Animals; D019328:Buthionine Sulfoximine / Q000494:pharmacology*; D004591:Electrophoresis, Polyacrylamide Gel; D005978:Glutathione / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000187:drug effects; D008668:Metallothionein / Q000096:biosynthesis / Q000187:drug effects; D009547:Nifurtimox / Q000494:pharmacology*; D009593:Nitroimidazoles / Q000494:pharmacology*; D015800:Protozoan Proteins / Q000096:biosynthesis / Q000187:drug effects*; D013095:Spermidine / Q000031:analogs & derivatives* / Q000096:biosynthesis; D013997:Time Factors; D014344:Trypanocidal Agents / Q000494:pharmacology*; D014349:Trypanosoma cruzi / Q000187:drug effects* / Q000378:metabolism
D009593:Nitroimidazoles; D015800:Protozoan Proteins; D014344:Trypanocidal Agents; D019328:Buthionine Sulfoximine; D008668:Metallothionein; C044809:trypanothione; D005978:Glutathione; D009547:Nifurtimox; D013095:Spermidine; C009999:benzonidazole