DOI . ORG {}
Title[redir]:
On the evolution of programmed cell death: apoptosis of the unicellular eukaryote Leishmania major involves cysteine proteinase activation and mitochondrion permeabilization | Cell Death & Differentiation
Description:
Leishmania major is a protozoan parasite from one of the most ancient phylogenic branches of unicellular eukaryotes, and containing only one giant mitochondrion. Here we report that staurosporine, that induces apoptosis in all mammalian nucleated cells, also induces in L. major a death process with several cytoplasmic and nuclear features of apoptosis, including cell shrinkage, phosphatidyl serine exposure, maintenance of plasma membrane integrity, mitochondrial transmembrane potential (ΔΨm) loss and cytochrome c release, nuclear chromatin condensation and fragmentation, and DNA degradation. Nuclear apoptosis-like features were prevented by cysteine proteinase inhibitors, and cell free assays using dying L. major cytoplasmic extracts indicated that the cysteine proteinases involved (i) also induced nuclear apoptosis-like features in isolated mammalian nuclei, and (ii) shared at least two nuclear substrates, but no cleavage site preference, with human effector caspases. Finally, isolated L. major mitochondria released cytochrome c and cysteine proteinases with nuclear pro-apoptotic activity when incubated with human recombinant Bax, even (although much less efficiently) when Bax was deleted of its transmembrane domain required for insertion in mitochondrial outermembranes, implying that L. major mitochondrion may express proteins able to interact with Bax. The recruitment of cysteine proteinases and mitochondria to the cell death machinery may be of very ancient evolutionary origin. Alternately, host/parasite interactions may have exerted selective pressures on the cell death phenotype of kinetoplastid parasites, resulting in the more recent emergence of an apoptotic machinery through a process of convergent evolution.
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Keywords {🔍}
cell, major, death, cells, article, nuclear, google, scholar, human, cas, bax, dna, apoptosis, figure, cytoplasmic, cysteine, promastigotes, cytochrome, mitochondria, staurosporine, mitochondrial, mammalian, extracts, proteinases, nuclei, features, induced, incubated, apoptotic, degradation, isolated, nature, release, mitochondrion, pcd, shown, induce, fragmentation, caspase, protein, baf, proteinase, membrane, parp, recombinant, control, unicellular, induces, absence, inhibitor,
Topics {✒️}
nature portfolio permissions reprints global leishmaniasis research development nature 407 horseradish-peroxidase-conjugated secondary antibodies ancestral metacaspase/paracaspase/caspase superfamily serine-proteinase inhibitor tosyl-lysylchloromethane golgi-localized sphingosine-1-phosphate phosphatase cathepsin inhibitor z-fa-fmk author information authors molecular nature potential nature apoptosis nature 407 forgotten nature 405 macrophages nature 403 baf/e64-inhibitable cysteine proteinase ice nature 371 host-parasite interaction parasitology nature castro-faria-neto hc agonistic anti-cd95 antibody secrete pro-inflammatory cytokines mouse monoclonal anti-parp caspase-independent executionary pathways original lysate volume aspartate-directed cysteine proteinases pro-apoptotic stimuli results caspase-independent pathway curr trans-epoxysuccinyl-l-leucylamido hopital bichat-claude bernard rabbit polyclonal anti-icad dictyostelium discoideum development author correspondence relative dna content caspase-mediated cell death bax channel-forming activity pro-apoptotic bcl-2 family time-dependent cell shrinkage cytochrome c-gfp fusion pro-apoptotic stimuli induce bak pro-apoptotic protein bcl-2/bax protein family nuclear pro-apoptotic activity human jurkat t-cells staurosporine-mediated cell death ceramide-induced apoptosis embo cysteine proteinase inhibitors 50 μg/ml creatine kinase anti-mammalian aif antibody dna content analyzed
Questions {❓}
- 2000 Calpain and caspases: can you tell the difference?
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headline:On the evolution of programmed cell death: apoptosis of the unicellular eukaryote Leishmania major involves cysteine proteinase activation and mitochondrion permeabilization
description:Leishmania major is a protozoan parasite from one of the most ancient phylogenic branches of unicellular eukaryotes, and containing only one giant mitochondrion. Here we report that staurosporine, that induces apoptosis in all mammalian nucleated cells, also induces in L. major a death process with several cytoplasmic and nuclear features of apoptosis, including cell shrinkage, phosphatidyl serine exposure, maintenance of plasma membrane integrity, mitochondrial transmembrane potential (ÎΨm) loss and cytochrome c release, nuclear chromatin condensation and fragmentation, and DNA degradation. Nuclear apoptosis-like features were prevented by cysteine proteinase inhibitors, and cell free assays using dying L. major cytoplasmic extracts indicated that the cysteine proteinases involved (i) also induced nuclear apoptosis-like features in isolated mammalian nuclei, and (ii) shared at least two nuclear substrates, but no cleavage site preference, with human effector caspases. Finally, isolated L. major mitochondria released cytochrome c and cysteine proteinases with nuclear pro-apoptotic activity when incubated with human recombinant Bax, even (although much less efficiently) when Bax was deleted of its transmembrane domain required for insertion in mitochondrial outermembranes, implying that L. major mitochondrion may express proteins able to interact with Bax. The recruitment of cysteine proteinases and mitochondria to the cell death machinery may be of very ancient evolutionary origin. Alternately, host/parasite interactions may have exerted selective pressures on the cell death phenotype of kinetoplastid parasites, resulting in the more recent emergence of an apoptotic machinery through a process of convergent evolution.
datePublished:2002-01-21T00:00:00Z
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cell death
apoptosis
mitochondria
DNA fragmentation
cysteine proteinase
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Cell Biology
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Cell Cycle Analysis
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headline:On the evolution of programmed cell death: apoptosis of the unicellular eukaryote Leishmania major involves cysteine proteinase activation and mitochondrion permeabilization
description:Leishmania major is a protozoan parasite from one of the most ancient phylogenic branches of unicellular eukaryotes, and containing only one giant mitochondrion. Here we report that staurosporine, that induces apoptosis in all mammalian nucleated cells, also induces in L. major a death process with several cytoplasmic and nuclear features of apoptosis, including cell shrinkage, phosphatidyl serine exposure, maintenance of plasma membrane integrity, mitochondrial transmembrane potential (ÎΨm) loss and cytochrome c release, nuclear chromatin condensation and fragmentation, and DNA degradation. Nuclear apoptosis-like features were prevented by cysteine proteinase inhibitors, and cell free assays using dying L. major cytoplasmic extracts indicated that the cysteine proteinases involved (i) also induced nuclear apoptosis-like features in isolated mammalian nuclei, and (ii) shared at least two nuclear substrates, but no cleavage site preference, with human effector caspases. Finally, isolated L. major mitochondria released cytochrome c and cysteine proteinases with nuclear pro-apoptotic activity when incubated with human recombinant Bax, even (although much less efficiently) when Bax was deleted of its transmembrane domain required for insertion in mitochondrial outermembranes, implying that L. major mitochondrion may express proteins able to interact with Bax. The recruitment of cysteine proteinases and mitochondria to the cell death machinery may be of very ancient evolutionary origin. Alternately, host/parasite interactions may have exerted selective pressures on the cell death phenotype of kinetoplastid parasites, resulting in the more recent emergence of an apoptotic machinery through a process of convergent evolution.
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cell death
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Cell Biology
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Apoptosis
Cell Cycle Analysis
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