Cell structure and cytokinesis alterations in multidrug-resistant Leishmania (Leishmania) amazonensis

Borges, Valéria M.; Lopes, Ulisses Gazos; Souza, Wanderley de; Vannier-Santos, Marcos A.

doi:10.1007/s00436-004-1248-8

Cited by 23 publications

(23 citation statements)

References 56 publications

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“…The supernumerary basal bodies in R72-treated parasites, as this structure orchestrates trypanosomatid parasite cell division and differentiation (Vaughan and Gull, 2016). Supernumerary centrosomes are indicative of cell pathology and drug-induced stress may cause the biogenesis of multiflagellate T. cruzi (Grellier et al., 1999) and Leishmania amazonensis (Borges et al., 2005). Hydrogen peroxide (Chae et al., 2005) and ROS-mediated autophagy (Pannu et al., 2012) are associated to centrosome amplification.…”

Section: Discussionmentioning

confidence: 99%

Effects of a novel β–lapachone derivative on Trypanosoma cruzi : Parasite death involving apoptosis, autophagy and necrosis

Anjos

Alves

Goncalves

et al. 2016

International Journal for Parasitology: Drugs and Drug Resistan

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Natural products comprise valuable sources for new antiparasitic drugs. Here we tested the effects of a novel β–lapachone derivative on Trypanosoma cruzi parasite survival and proliferation and used microscopy and cytometry techniques to approach the mechanism(s) underlying parasite death. The selectivity index determination indicate that the compound trypanocidal activity was over ten-fold more cytotoxic to epimastigotes than to macrophages or splenocytes. Scanning electron microscopy analysis revealed that the R72 β–lapachone derivative affected the T. cruzi morphology and surface topography. General plasma membrane waving and blebbing particularly on the cytostome region were observed in the R72-treated parasites. Transmission electron microscopy observations confirmed the surface damage at the cytostome opening vicinity. We also observed ultrastructural evidence of the autophagic mechanism termed macroautophagy. Some of the autophagosomes involved large portions of the parasite cytoplasm and their fusion/confluence may lead to necrotic parasite death. The remarkably enhanced frequency of autophagy triggering was confirmed by quantitating monodansylcadaverine labeling. Some cells displayed evidence of chromatin pycnosis and nuclear fragmentation were detected. This latter phenomenon was also indicated by DAPI staining of R72-treated cells. The apoptotis induction was suggested to take place in circa one-third of the parasites assessed by annexin V labeling measured by flow cytometry. TUNEL staining corroborated the apoptosis induction. Propidium iodide labeling indicate that at least 10% of the R72-treated parasites suffered necrosis within 24 h. The present data indicate that the β–lapachone derivative R72 selectively triggers T. cruzi cell death, involving both apoptosis and autophagy-induced necrosis.

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Section: Discussionmentioning

confidence: 99%

Effects of a novel β–lapachone derivative on Trypanosoma cruzi : Parasite death involving apoptosis, autophagy and necrosis

Anjos

Alves

Goncalves

et al. 2016

International Journal for Parasitology: Drugs and Drug Resistan

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“…Moreover, it is well established that in these parasites, progression throughout the cell cycle is dependent on microtubule-mediated events, and interfering with microtubule polymerization/depolymerization has been shown to affect basal body duplication, kinetoplast segregation, flagellar axoneme growth, mitosis, cell growth, and cytokinesis of trypanosomes (16,(22)(23)(24)35). Microtubule-mediated events also play major roles in progression of the Leishmania cell cycle (4,12,13), and treatment of Leishmania promastigotes with antimicrotubule agents re-sulted in inhibition of nuclear mitosis and cytokinesis and inaccurate positioning of the kinetoplast within the cell (11).…”

mentioning

confidence: 99%

Morphological Events during the Cell Cycle of Leishmania major

et al. 2011

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The morphological events involved in the Leishmania major promastigote cell cycle have been investigated in order to provide a detailed description of the chronological processes by which the parasite replicates its set of single-copy organelles and generates a daughter cell. Immunofluorescence labeling of ␤-tubulin was used to follow the dynamics of the subcellular cytoskeleton and to monitor the division of the nucleus via visualization of the mitotic spindle, while RAB11 was found to be a useful marker to track flagellar pocket division and to follow mitochondrial DNA (kinetoplast) segregation. Classification and quantification of these morphological events were used to determine the durations of phases of the cell cycle. Our results demonstrate that in L. major promastigotes, the extrusion of the daughter flagellum precedes the onset of mitosis, which in turn ends after kinetoplast segregation, and that significant remodelling of cell shape accompanies mitosis and cytokinesis. These findings contribute to a more complete foundation for future studies of cell cycle control in Leishmania.Leishmania spp. are protozoan parasites that are the causative agents of the leishmaniases, a spectrum of vector-borne diseases endemic in tropical and subtropical countries. The cutaneous form of leishmaniasis is the most common form, and it is estimated that it afflicts about 10 million people. In Africa and Asia, this disease is caused mainly by Leishmania tropica and L. major. The two major replicative developmental stages in the life cycle of Leishmania are the procyclic promastigote, which occurs in the sand fly insect vector, and the amastigote, which resides in the phagolysosome of mammalian macrophages. Leishmania procyclic promastigotes are highly polarized cells that possess a number of single-copy organelles with defined subcellular locations. These include the nucleus, the Golgi apparatus, the basal body, the mitochondrion (which incorporates the kinetoplast), and the flagellum, which protrudes from the cell body via the flagellar pocket. The generation of viable progeny relies upon precise control of the duplication and segregation of these organelles (11,17,29,32).The cell cycle of procyclic form Trypanosoma brucei has been characterized extensively and forms a basis for comparison with other trypanosomatids, including Leishmania. Notably, in T. brucei, replication of the nuclear and kinetoplast DNAs (S phase) starts almost synchronously, whereas the division and segregation periods for the nucleus (M and C phases, respectively) and kinetoplast (D and A phases, respectively) are separated in time. In procyclic form T. brucei as well as in L. tarentolae (28), kinetoplast division is completed before the onset of nuclear mitosis, while in L. mexicana and L. donovani these events appear to occur in the reverse order (11,17,32). The chromosomes of T. brucei do not visibly condense, the nuclear envelope remains intact during mitosis, and no structural equivalents of the mammalian spindle pole bodies (centrosomes) hav...

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“…cruzi trypomastigotes treated with suramin exhibited an altered nuclear division pattern and frequently presented irregular or multiple nuclei [92]. Vinblastin-resistant L. amazonensis also presented dysfunctional cytokinesis, in which the resistant promastigotes showed multiple nuclei [93]. This characteristic was found in parasites treated with the squalene synthase inhibitors BPQ-OH, ER-119884 and E5700; promastigotes were frequently multinucleate (Fig.…”

Section: Nucleusmentioning

confidence: 86%

“…Vinblastine treatment also caused Leishmania ER cisternae to protrude outward and to contact the plasma membrane [93].…”

Section: Endoplasmic Reticulum and Golgi Complexmentioning

confidence: 99%

Contributions of Ultrastructural Studies to the Cell Biology of Trypanosmatids: Targets for Anti-Parasitic Drugs

Almeida¹,

Souto-Padrón

2010

TOPARAJ

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Protozoan parasites cause disease in humans worldwide, and many fall into the genera Trypanosoma and Leishmania; these parasites are responsible for African trypanosomiasis, Chagas disease and the different forms of Leishmaniasis. Strategies for the development of new drugs against these protozoans have been based on their cell biology and biochemistry complemented by the use of electron microscopy. Trypanosoma and Leishmania have special organelles that are involved in metabolic pathways, which are very distinct from those in mammalian cells; these organelles are potential drug targets. Scanning and transmission electron microscopy can identify not only the target organelles but also alterations to the cell surface and ultrastructural changes that characterize distinct forms of programmed cell death.

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Cell structure and cytokinesis alterations in multidrug-resistant Leishmania (Leishmania) amazonensis

Cited by 23 publications

References 56 publications

Effects of a novel β–lapachone derivative on Trypanosoma cruzi : Parasite death involving apoptosis, autophagy and necrosis

Effects of a novel β–lapachone derivative on Trypanosoma cruzi : Parasite death involving apoptosis, autophagy and necrosis

Morphological Events during the Cell Cycle of Leishmania major

Contributions of Ultrastructural Studies to the Cell Biology of Trypanosmatids: Targets for Anti-Parasitic Drugs

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