Literature DB >> 1829686

Disruption of mitochondrial function as the basis of the trypanocidal effect of trifluoperazine on Trypanosoma cruzi.

J L Lacuara1, S R de Barioglio, P P de Oliva, A S Bernacchi, A F de Culasso, J A Castro, B M Franke de Cazzulo, J J Cazzulo.   

Abstract

The tricyclic anti-calmodulin drug trifluoperazine (TFP) inhibited growth and motility of epimastigotes of Trypanosoma cruzi, at concentrations lower than 100 microM, and motility and infectivity of the bloodstream trypomastigote form at 200 microM. Electron microscopy of TFP-treated epimastigotes showed that the major effect was at the mitochondrial level, with gross swelling and disorganization. The oligomycin-sensitive, mitochondrial ATPase was completely inhibited by 20 microM TFP, and the same drug concentration caused a 60% decrease in intracellular ATP content. The results suggest that the trypanocidal effect of TFP may be related more to mitochondrial damage than to the well-known anticalmodulin effect of the drug.

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Year:  1991        PMID: 1829686     DOI: 10.1007/bf01949887

Source DB:  PubMed          Journal:  Experientia        ISSN: 0014-4754


  19 in total

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Authors:  B R Bloom
Journal:  Nature       Date:  1979-05-03       Impact factor: 49.962

2.  Effects of calmodulin antagonists on the active Ca2+ uptake by rat liver mitochondria.

Authors:  M G Vale; A J Moreno; A P Carvalho
Journal:  Biochem J       Date:  1983-09-15       Impact factor: 3.857

3.  Inhibition of calmodulin by phenothiazines and related drugs: structure-activity relationships.

Authors:  W C Prozialeck; B Weiss
Journal:  J Pharmacol Exp Ther       Date:  1982-09       Impact factor: 4.030

4.  Identification of calmodulin in mitochondria from rat liver: a possible role in regulation of the oligomycin sensitive ATPase.

Authors:  L Ruben; D B Goodman; H Rasmussen
Journal:  Ann N Y Acad Sci       Date:  1980       Impact factor: 5.691

5.  Protonmotive force-driven active transport of D-glucose and L-proline in the protozoan parasite Leishmania donovani.

Authors:  D Zilberstein; D M Dwyer
Journal:  Proc Natl Acad Sci U S A       Date:  1985-03       Impact factor: 11.205

6.  Selective antimitochondrial agents inhibit calmodulin.

Authors:  W L Bodden; S T Palayoor; W N Hait
Journal:  Biochem Biophys Res Commun       Date:  1986-03-13       Impact factor: 3.575

7.  Adhesion and interiorization of Trypanosoma cruzi in mammalian cells.

Authors:  N W Andrews; W Colli
Journal:  J Protozool       Date:  1982-05

Review 8.  Interaction of drugs with calmodulin. Biochemical, pharmacological and clinical implications.

Authors:  B Weiss; W C Prozialeck; T L Wallace
Journal:  Biochem Pharmacol       Date:  1982-07-01       Impact factor: 5.858

9.  Calmodulin binding proteins in rat liver mitochondria.

Authors:  P Gazzotti; M Gloor; E Carafoli
Journal:  Biochem Biophys Res Commun       Date:  1984-02-29       Impact factor: 3.575

10.  Calmodulin and Ca2+-dependent cyclic AMP phosphodiesterase activity in Trypanosoma cruzi.

Authors:  M T Téllez-Iñón; R M Ulloa; M Torruella; H N Torres
Journal:  Mol Biochem Parasitol       Date:  1985-11       Impact factor: 1.759

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  1 in total

1.  Susceptibility of melanized and nonmelanized Cryptococcus neoformans to the melanin-binding compounds trifluoperazine and chloroquine.

Authors:  Y Wang; A Casadevall
Journal:  Antimicrob Agents Chemother       Date:  1996-03       Impact factor: 5.191

  1 in total

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