4.3 Article

Mechanism of Trypanosoma cruzi death induced by Cratylia mollis seed lectin

Journal

JOURNAL OF BIOENERGETICS AND BIOMEMBRANES
Volume 42, Issue 1, Pages 69-78

Publisher

SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s10863-010-9268-9

Keywords

Trypanosoma cruzi; Mitochondria; Calcium; ROS; Cell death; Cramoll 1,4 lectin

Funding

  1. Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)
  2. Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)
  3. Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)

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Incubation of T. cruzi epimastigotes with the lectin Cramoll 1,4 in Ca2+ containing medium led to agglutination and inhibition of cell proliferation. The lectin (50 A mu g/ml) induced plasma membrane permeabilization followed by Ca2+ influx and mitochondrial Ca2+ accumulation, a result that resembles the classical effect of digitonin. Cramoll 1,4 stimulated (five-fold) mitochondrial reactive oxygen species (ROS) production, significantly decreased the electrical mitochondrial membrane potential (Delta I-m) and impaired ADP phosphorylation. The rate of uncoupled respiration in epimastigotes was not affected by Cramoll 1,4 plus Ca2+ treatment, but oligomycin-induced resting respiration was 65% higher in treated cells than in controls. Experiments using T. cruzi mitochondrial fractions showed that, in contrast to digitonin, the lectin significantly decreased Delta I-m by a mechanism sensitive to EGTA. In agreement with the results showing plasma membrane permeabilization and impairment of oxidative phosphorylation by the lectin, fluorescence microscopy experiments using propidium iodide revealed that Cramoll 1,4 induced epimastigotes death by necrosis.

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