Disruption of Ca2+ homeostasis in Trypanosoma cruzi by crystal violet.
We have demonstrated previously that crystal violet induces a rapid, dose-related collapse of the inner mitochondrial membrane potential of Trypanosoma cruzi epimastigotes. In this work, we show that crystal violet-induced dissipation of the membrane potential was accompanied by an efflux of Ca2+ from the mitochondria. In addition, crystal violet inhibited the ATP-dependent, oligomycin-, and antimycin A-insensitive Ca2+ uptake by digitonin-permeabilized epimastigotes. Crystal violet also induced Ca2+ release from the mitochondria and endoplasmic reticulum of digitonin-permeabilized trypomastigotes. Furthermore, crystal violet inhibited Ca2+ uptake and the (Ca(2+)-Mg2+)-ATPase of a highly enriched plasma membrane fraction of epimastigotes, thus indicating an inhibition of other calcium transport mechanisms of the cells. Disruption of Ca2+ homeostasis by crystal violet may be a key process leading to trypanosome cell injury by this drug.
Docampo
R
R
Department of Veterinary Pathobiology, University of Illinois, Urbana 61801.
Gadelha
F R
FR
Moreno
S N
SN
Benaim
G
G
Hoffmann
M E
ME
Vercesi
A E
AE
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D005840:Gentian Violet / Q000494:pharmacology*; D006706:Homeostasis / Q000187:drug effects; D014349:Trypanosoma cruzi / Q000187:drug effects* / Q000378:metabolism
D005840:Gentian Violet; D002118:Calcium