Different cell death pathways induced by drugs in Trypanosoma cruzi: An ultrastructural study

Menna-Barreto, Rubem F.S.; Salomão, Kelly; Dantas, A.P.; Santa‐Rita, Ricardo M.; Soares, Maurílio J.; Barbosa, Helene Santos; Castro, Solange L. de

doi:10.1016/j.micron.2008.08.003

Cited by 140 publications

(130 citation statements)

References 97 publications

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“…For T. brucei, the example is the killing of parasites as a result of administration of DHA or neuropeptides, 120,121 while for T. cruzi the same was achieved with lysophospholipid analogues and naphtoimidazoles. 127,130 However, similar data regarding the induction of autophagic cell death of Leishmania parasites by administration of compounds are not available.…”

Section: Discussionmentioning

confidence: 99%

“…127,128 Ultrastructural studies in epimastigotes and trypomastigotes treated with either one of three naphthoimidazoles N1, N2 and N3 derived from β-lapachone demonstrate that the mitochondrion, Golgi and reservosomes are the main targets. 128,129 Frequently, treatment with these three compounds induces morphological autophagic characteristics in the parasites such as the occurrence of concentric membrane structures in the cytosol and an increase in the number of autophagosome-like bodies, observations reinforced by the strong increase of monodansylcadaverine labeling.…”

Section: O N O T D I S T R I B U T Ementioning

confidence: 99%

“…126 Other trypanocidal agents such as the dinitroanilines trifluralin and chloralin lead to the appearance of vacuoles containing damaged membranes. 127 Also some natural products such as geranylgeraniol, propolis and naphthoquinones The parasites showed well-developed endoplasmic reticulum profiles (black arrows) surrounding organelles, especially reservosomes (R), suggesting a close contact between both membranes (black arrowheads), and commonly loss of the integrity of these organelle structures (white arrowheads). (C) A cytoplasmic vesicle near to a reservosome was also observed, suggesting fusion with the organelle (white arrows).…”

Section: O N O T D I S T R I B U T Ementioning

confidence: 99%

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Autophagy in protists

et al. 2011

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Autophagy is the degradative process by which eukaryotic cells digest their own components using acid hydrolases within the lysosome. Originally thought to function almost exclusively in providing starving cells with nutrients taken from their own cellular constituents, autophagy is in fact involved in numerous cellular events including differentiation, turnover of macromolecules and organelles, and defense against parasitic invaders. During the last 10-20 years, molecular components of the autophagic machinery have been discovered, revealing a complex interactome of proteins and lipids, which, in a concerted way, induce membrane formation to engulf cellular material and target it for lysosomal degradation. Here, our emphasis is autophagy in protists. We discuss experimental and genomic data indicating that the canonical autophagy machinery characterized in animals and fungi appeared prior to the radiation of major eukaryotic lineages. Moreover, we describe how comparative bioinformatics revealed that this canonical machinery has been subject to moderation, outright loss or elaboration on multiple occasions in protist lineages, most probably as a consequence of diverse lifestyle adaptations. We also review experimental studies illustrating how several pathogenic protists either utilize autophagy mechanisms or manipulate host-cell autophagy in order to establish or maintain infection within a host. The essentiality of autophagy for the pathogenicity of many parasites, and the unique features of some of the autophagy-related proteins involved, suggest possible new targets for drug discovery. Further studies of the molecular details of autophagy in protists will undoubtedly enhance our understanding of the diversity and complexity of this cellular phenomenon and the opportunities it offers as a drug target

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Section: Discussionmentioning

confidence: 99%

Section: O N O T D I S T R I B U T Ementioning

confidence: 99%

Section: O N O T D I S T R I B U T Ementioning

confidence: 99%

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Autophagy in protists

et al. 2011

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“…Interestingly, autophagic (autophagosomes), apoptoticlike (membrane blebbing) phenotypes, and necrosis have been reported in Naphthoimidazoles-treated Trypanosoma cruzi [1]. It has been demonstrated that an intense cross-talking between autophagy, apoptosis, and necrosis in the protozoa in response to diverse drug stimuli that cover the same pathway of the previous processes [2]. Intriguingly, in the light of the fact that apoptosis and autophagy are interconnected, a significant analysis and discussion on the proteins with a dual role in autophagy and apoptosis were presented by Li et al and Tait et al [3,4].…”

Section: Introductionmentioning

confidence: 99%

Cell death offers exceptional cellular and molecular windows for pharmacological interventions in protozoan parasites

El‐Ashram¹,

Mehmood²,

Dinçel³

et al. 2017

Integr Mol Med

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The rich repertoire of cell death events is a crucial biological process that deserves extensive review at a formative time for the development of our knowledge concerning the state-of-the-art data on their cellular and molecular mechanisms of action and the ways in which they can be manipulated in and by protozoan parasites. We have attempted to provide a comprehensive overview to reveal intervention points that could be exploited to discover novel therapies, vaccine strategies and prophylactic intervention points for protozoan parasites, and to understand the parasitic disease progression and the infection consequence.

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“…Azithromycin induced dramatic morphological alterations in the parasite structure and induced plasma membrane distortion till total destruction and parasite lyses. The formation of large vacuoles followed by a total destruction of the cell strongly suggests an autophagic-like or necrotic mechanism of cell death (Bera et al 2003;Menna-Barreto et al 2009;Marr et al 2012). In fact, unlike apoptosis, autophagic cell death is a process characterized by the accumulation of autophagic vacuoles in the cytoplasm accompanied by extensive degradation of the Golgi apparatus, the polyribosomes and the endoplasmic reticulum, which precedes the destruction of the nucleus (Lefranc et al 2007).…”

Section: Discussionmentioning

confidence: 99%