Programmed Cell Death in Procyclic Form Trypanosoma brucei rhodesiense - Identification of Differentially Expressed Genes during Con A Induced Death

Welburn, Susan C.; Lillico, Simon; Murphy, Noel B.

doi:10.1590/s0074-02761999000200020

Cited by 46 publications

(31 citation statements)

References 37 publications

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“…23 In T. brucei procyclic forms, similar morphological features of apoptosis could be induced, in vitro, with concanavalin A treatment, 24,25 or under oxidative stress. 26 Additionally, Leishmania amazonensis promastigotes display DNA laddering and chromatin condensation in dense clusters (leading to the breakdown of the nuclear membrane) upon heat-shock, corresponding to classical features of PCD.…”

Section: Introductionmentioning

confidence: 98%

“…In dying Trypanosoma cruzi epimastigotes, elongation factor 1-alpha was shown to relocalise from the cytoplasm into the nucleus 28 whereas in Trypanosoma brucei rhodesiense, prohibitin, an homologue of a mammalian protooncogene and RACK, a receptor for activated protein kinase C, were shown to be up-regulated in procyclic Trypanosoma induced to undergo cell death. 25,29 In Tetrahymena and in Stylonychia, morphological changes and proteins possibly involved in programmed DNA degradation have been described. 8,12,30 However, none of these reports provide answers about the implicated pathways except in the case of death in Trypanosoma brucei, which was shown to be Ca 2+ -dependent when induced by reactive oxygen species (ROS).…”

Section: Introductionmentioning

confidence: 99%

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Cell death in Leishmania induced by stress and differentiation: programmed cell death or necrosis?

2002

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Unicellular organisms, such as the protozoan parasite Leishmania, can be stimulated to show some morphological and biochemical features characteristic of mammalian apoptosis. This study demonstrates that under a variety of stress conditions such as serum deprivation, heat shock and nitric oxide, cell death can be induced leading to genomic DNA fragmentation into oligonucleosomes. DNA fragmentation was observed, without induction, in the infectious stages of the parasite, and correlated with the presence of internucleosomal nuclease activity, visualisation of 45 to 59 kDa nucleases and detection of TUNEL-positive nuclei. DNA fragmentation was not dependent on active effector downstream caspases nor on the lysosomal cathepsin L-like enyzmes CPA and CPB. These data are consistent with the presence of a caspase-independent cell death mechanism in Leishmania, induced by stress and differentiation that differs significantly from metazoa.

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Section: Introductionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Cell death in Leishmania induced by stress and differentiation: programmed cell death or necrosis?

2002

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“…Apoptosis, a morphologically distinct form of cell death that is crucial for embryogenesis, tissue homeostasis, and disease control in metazoans, has also been demonstrated in unicellular organisms including yeast and protozoan parasites (1)(2)(3)(4)(5)(6). The protozoan parasites have a digenic life cycle, residing as flagellated extracellular promastigotes in the gut of the insect vector or as obligatory intracellular amastigotes found in the parasitophorous vacuoles of mammalian macrophages.…”

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confidence: 99%

Antimonial-induced Increase in Intracellular Ca2+ through Non-selective Cation Channels in the Host and the Parasite Is Responsible for Apoptosis of Intracellular Leishmania donovani Amastigotes

Sudhandiran

Shaha

2003

Journal of Biological Chemistry

155

126

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The capability of the obligate intracellular parasites like Leishmania donovani to survive within the host cell parasitophorous vacuoles as nonmotile amastigotes determines disease pathogenesis, but the mechanism of elimination of the parasites from these vacuoles are not well understood. By using the anti-leishmanial drug potassium antimony tartrate, we demonstrate that, upon drug exposure, intracellular L. donovani amastigotes undergo apoptotic death characterized by nuclear DNA fragmentation and externalization of phosphatidylserine. Changes upstream of DNA fragmentation included generation of reactive oxygen species like superoxide, nitric oxide, and hydrogen peroxide that were primarily concentrated in the parasitophorous vacuoles. In the presence of antioxidants like N-acetylcysteine or Mn(III) tetrakis(4-benzoic acid)porphyrin chloride, an inhibitor of inducible nitric-oxide synthase, a diminution of reactive oxygen species generation and improvement of amastigote survival were observed, suggesting a close link between drug-induced oxidative stress and amastigote death. Changes downstream to reactive oxygen species increase involved elevation of intracellular Ca 2؉ concentrations in both the parasite and the host that was preventable by antioxidants. Flufenamic acid, a non-selective cation channel blocker, decreased the elevation of Ca 2؉ in both the cell types and reduced amastigote death, thus establishing a central role of Ca 2؉ in intracellular parasite clearance. This influx of Ca 2؉ was preceded by a fall in the amastigote mitochondrial membrane potential. Therefore, this study projects the importance of flufenamic acid-sensitive non-selective cation channels as important modulators of antimonial efficacy and lends credence to the suggestion that, within the host cell, apoptosis is the preferred mode of death for the parasites.

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“…DDRT-PCR has been used to better define pathogen-host interactions. Studies with nonfungal pathogens have included comparison of virulent and nonvirulent strains (51,118,119), studies of the transition from colonization to disease (29,115,132), differential expression of pathogen genes (1) or host genes (78,112,113) after invasion, effects of drugs on pathogens (138), and pathogen cell death (151).…”

Section: Microbial Pathogenesis (Nonfungal)mentioning

confidence: 99%

“…An understanding of the mechanisms of apoptosis in pathogens may result in novel antimicrobial therapies or pathogen control. Trypanosoma brucei rhodesiense undergoes apoptosis after stimulation with concanavalin A, and this process is associated with de novo gene expression (151). Therefore, apoptosis may be directly controlled by the induction of several genes that are normally expressed at a very low level; however, it is also possible that housekeeping genes are also important in this event.…”

Section: Drug and Environmental Influencesmentioning

confidence: 99%

Applications of Differential-Display Reverse Transcription-PCR to Molecular Pathogenesis and Medical Mycology

Sturtevant

2000

Clinical Microbiology Reviews

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Programmed Cell Death in Procyclic Form Trypanosoma brucei rhodesiense - Identification of Differentially Expressed Genes during Con A Induced Death

Cited by 46 publications

References 37 publications

Cell death in Leishmania induced by stress and differentiation: programmed cell death or necrosis?

Cell death in Leishmania induced by stress and differentiation: programmed cell death or necrosis?

Antimonial-induced Increase in Intracellular Ca2+ through Non-selective Cation Channels in the Host and the Parasite Is Responsible for Apoptosis of Intracellular Leishmania donovani Amastigotes

Applications of Differential-Display Reverse Transcription-PCR to Molecular Pathogenesis and Medical Mycology

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