The reservosome of Trypanosoma cruzi epimastigotes: an organelle of the endocytic pathway with a role on metacyclogenesis

Soares, Maurílio J.

doi:10.1590/s0074-02761999000700015

Cited by 32 publications

(27 citation statements)

References 15 publications

(13 reference statements)

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“…To further investigate the reservosome damage, treated parasites were analyzed by flow cytometry and fluorescence microscopy using AO, an established marker of acidic compartments in trypanosomatids (Soares 1999;PortoCarreiro et al 2000;Docampo and Moreno 2001). N2 and N3 induced a decrease in fluorescence of AO in both forms of T. cruzi.…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial disruption and DNA fragmentation in Trypanosoma cruzi induced by naphthoimidazoles synthesized from β-lapachone

et al. 2007

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Three naphthoimidazoles presenting aromatic groups attached to the imidazole ring were the most active against trypomastigotes of Trypanosoma cruzi between 45 derivatives from beta-lapachone. N1 is active against the three forms of the parasite. In this work, we investigated N2 and N3 and analyzed the effect of the three derivatives on metacyclogenesis, endocytosis, and cell cycle. In epimastigotes, N2 and N3 blocked the cell cycle, inhibited succinate cytochrome c reductase, metacyclogenesis, and induced damage to mitochondrion, Golgi, and reservosomes. In treated trypomastigotes, there were alterations in the mitochondrion, nucleus and kinetoplast, and DNA fragmentation. Preincubation with cysteine protease inhibitors reversed the effect of N1, N2, and N3. Such reversion and ultrastructural alterations suggest the involvement of autophagy in parasite death. Ultrastructural, flow cytometry, and biochemical studies suggest that naphthoimidazoles interferes with the energetic metabolism and induces DNA fragmentation.

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Section: Discussionmentioning

confidence: 99%

Mitochondrial disruption and DNA fragmentation in Trypanosoma cruzi induced by naphthoimidazoles synthesized from β-lapachone

et al. 2007

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“…The presence of heterogeneous forms and large electron-lucent inclusions in the reservosomes after treatment with Et-Blg has been already reported in the DM28 clone of T. cruzi, suggesting a rupture of the organelle (De Souza et al 2002). Since reservosomes are acidic storage compartments in epimastigotes (Soares 1999), decrease in the electron-density of the matrix of these organelles in Et-Blg-treated parasites suggests a possible interference in the content of lipids and proteins.…”

Section: Discussionmentioning

confidence: 99%

The effect of Bulgarian propolis against Trypanosoma cruzi and during its interaction with host cells

Dantas

Salomão

Barbosa

et al. 2006

Mem. Inst. Oswaldo Cruz

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Propolis has shown activity against pathogenic microorganisms that cause diseases in humans and animals. The ethanol (Et-Blg) and acetone (Ket-Blg) extracts from a Bulgarian propolis, with known chemical compositions, presented similar activity against tissue culture-derived amastigotes. The treatment of Trypanosoma cruzi-infected skeletal muscle cells with Et-Blg led to a decrease of infection and of the intracellular proliferation of amastigotes, while damage to the host cell was observed only at concentration 12.5 times higher than those affecting the parasite. Ultrastructural analysis of the effect of both extracts in epimastigotes revealed that the main targets were the mitochondrion and reservosomes. Et-Blg also affected the mitochondrion-kinetoplast complex in trypomastigotes, offering a potential target for chemotherapeutic agents.Key words: propolis -natural products -Trypanosoma cruzi -Chagas disease Chagas disease, caused by the trypanosomatid protozoan Trypanosoma cruzi, is endemic in Latin America. Initially restricted to natural ecotopes, with transmission among small autochthonous mammals by hematophagous Triatominae bugs, the occupation by humans of such ecotopes led to the establishment of the vectors in human dwellings, changing the characteristic of the disease from zoonotic to antropozoonotic. In humans, the acute phase results in 2-8% mortality, specially among children, while in the chronic phase most patients remain asymptomatic and about 30 to 40% of the cases develop symptoms of cardiac or digestive lesions. The World Health Organization estimates that about 18 million people are infected with T. cruzi (WHO 2002). The available drugs for the clinical treatment, the nitroderivatives benznidazole and nifurtimox, are unsatisfactory. They present variable healing effects during the acute phase according to the geographical region and require long term treatment, besides presenting frequent toxic side effects and limited efficacy in the chronic stage (reviewed in Coura & De Castro 2001).In this context, there is an intense search for new synthetic compounds and natural products for treatment of Chagas disease. Thus, our group has been engaged in experimental chemotherapy studies using propolis (Higashi & De Castro 1994, De Castro & Higashi 1995, Marcucci et al. 2001, Prytzyk et al. 2003, Paulino et al. 2003, Salomão et al. 2004). Propolis, a bee product collected from different plant exudates, is a complex mixture containing known bioactive constituents, such as flavonoids, phenolic acids and esters, terpenes, sesquiterpenes, aromatic aldehydes, and alcohols (Marcucci 1995). In temperate zones, bud exudates from poplar trees (Populus spp.) are the main source of flavonoid-rich propolis, which are rich in flavonoids (reviewed in Bankova et al. 2000).During the last decades, an increasing number of studies on the chemical composition, biological activity, and therapeutic uses of propolis has been published (reviewed in De Castro 2001). In recent studies with a Bulgarian propolis sample, we ...

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“…However, other ultrastructural effects were also observed for this drug, and could also be important in growth inhibition. For example, the early effects of Ris on the reservosomes, which are involved in endocytosis, storage and breakdown of nutrients [36,45], could hamper the proliferation process in epimastigotes. Although the precise molecular mechanisms of these effects are doubtless complex and at this time remain obscure, they could be related to altered protein synthesis and sorting associated with abnormal cell signalling, due to a depletion of essential poly-isoprenoids.…”

Section: Discussionmentioning

confidence: 99%

“…cruzi epimastigotes contain characteristic membranebound organelles called reservosomes, which are terminal vesicles of the cell's endocytic pathway and have a protein-rich matrix, together with lipid droplets [36]. Reservosomes were among the first organelles altered by treatment with Ris (Fig.…”

Section: Effects Of Risedronate On T Cruzi Epimastigotesmentioning

confidence: 99%

Selective in vitro effects of the farnesyl pyrophosphate synthase inhibitor risedronate on Trypanosoma cruzi

Garzoni

Caldera

Meirelles

et al. 2004

International Journal of Antimicrobial Agents

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The reservosome of Trypanosoma cruzi epimastigotes: an organelle of the endocytic pathway with a role on metacyclogenesis

Cited by 32 publications

References 15 publications

Mitochondrial disruption and DNA fragmentation in Trypanosoma cruzi induced by naphthoimidazoles synthesized from β-lapachone

Mitochondrial disruption and DNA fragmentation in Trypanosoma cruzi induced by naphthoimidazoles synthesized from β-lapachone

The effect of Bulgarian propolis against Trypanosoma cruzi and during its interaction with host cells

Selective in vitro effects of the farnesyl pyrophosphate synthase inhibitor risedronate on Trypanosoma cruzi

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