ArticleCell death & disease2010
Cathepsin B-like and cell death in the unicellular human pathogen Leishmania.
Article in Cell death & disease, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
26 citing papers in PubMed, 44 citations in OpenAlex.
- Highlights in Cysteine Protease Inhibitors as Antiparasitic Agents Against Trypanosomatids.International journal of molecular sciences · 2026Review
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- An inclusive assessment of apoptosis mechanisms inCurrent research in parasitology & vector-borne diseases · 2025Review
- Cell Death in Cyanobacteria: Current Understanding and Recommendations for a Consensus on Its Nomenclature.Frontiers in microbiology · 2021Review
- A potential acetyltransferase involved in Leishmania major metacaspase-dependent cell death.Parasites & vectors · 2019Article
- Cell death in Leishmania.Parasite (Paris, France) · 2019Review
- Cysteine proteases in protozoan parasites.PLoS neglected tropical diseases · 2018Review
- Different apoptosis pathways inCell death discovery · 2018Article
- Zinc depletion promotes apoptosis-like death in drug-sensitive and antimony-resistance Leishmania donovani.Scientific reports · 2017Article
- Methionine aminopeptidase 2 is a key regulator of apoptotic like cell death in Leishmania donovani.Scientific reports · 2017Article
- Metacaspase-binding peptide inhibits heat shock-induced death in Leishmania (L.) amazonensis.Cell death & disease · 2017Article
- The calpain inhibitor MDL28170 induces the expression of apoptotic markers in Leishmania amazonensis promastigotes.PloS one · 2014Article
- The first suicides: a legacy inherited by parasitic protozoans from prokaryote ancestors.Parasites & vectors · 2013Review
- Apoptotic marker expression in the absence of cell death in staurosporine-treated Leishmania donovani.Antimicrobial agents and chemotherapy · 2013Article
- Cell death in parasitic protozoa: regulated or incidental?Nature reviews. Microbiology · 2013Review
- Cathepsin B gene disruption induced Leishmania donovani proteome remodeling implies cathepsin B role in secretome regulation.PloS one · 2013Article
- Identification of semicarbazones, thiosemicarbazones and triazine nitriles as inhibitors of Leishmania mexicana cysteine protease CPB.PloS one · 2013Article
- Analysis of apoptosis methods recently used in Cancer Research and Cell Death & Disease publications.Cell death & disease · 2012Article
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Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
In several studies reporting cell death (CD) in lower eukaryotes and in the human protozoan parasite Leishmania, proteolytic activity was revealed using pan-caspase substrates or inhibitors such as carbobenzoxy-valyl-alanyl-aspartyl-[O-methyl]-fluoromethylketone (Z-VAD-FMK). However, most of the lower eukaryotes do not encode caspase(s) but MCA, which differs from caspase(s) in its substrate specificity and cannot be accountable for the recognition of Z-VAD-FMK. In the present study, we were interested in identifying which enzyme was capturing the Z-VAD substrate. We show that heat shock (HS) induces Leishmania CD and leads to the intracellular binding of Z-VAD-FMK. We excluded binding and inhibition of Z-VAD-FMK to Leishmania major metacaspase (LmjMCA), and identified cysteine proteinase C (LmjCPC), a cathepsin B-like (CPC) enzyme, as the Z-VAD-FMK binding enzyme. We confirmed the specific interaction of Z-VAD-FMK with CPC by showing that Z-VAD binding is absent in a Leishmania mexicana strain in which the cpc gene was deleted. We also show that parasites exposed to various stress conditions release CPC into a soluble fraction. Finally, we confirmed the role of CPC in Leishmania CD by showing that, when exposed to the oxidizing agent hydrogen peroxide (H(2)O(2)), cpc knockout parasites survived better than wild-type parasites (WT). In conclusion, this study identified CPC as the substrate of Z-VAD-FMK in Leishmania and as a potential additional executioner protease in the CD cascade of Leishmania and possibly in other lower eukaryotes.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.