ArticleAntimicrobial agents and chemotherapy2013
Apoptotic marker expression in the absence of cell death in staurosporine-treated Leishmania donovani.
Article in Antimicrobial agents and chemotherapy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 23 citations in OpenAlex.
- SystematicFrontiers in chemistry · 2021Article
- Antikinetoplastid Activity of Indolocarbazoles fromBiomolecules · 2020Article
- Tocopherol biosynthesis inFEBS open bio · 2019Article
- Synthesis, characterization, and mechanistic studies of a gold nanoparticle-amphotericin B covalent conjugate with enhanced antileishmanial efficacy and reduced cytotoxicity.International journal of nanomedicine · 2019Article
- Temporal analysis of the autophagic and apoptotic phenotypes inMicrobial cell (Graz, Austria) · 2018Article
- Ammonium trichloro [1,2-ethanediolato-O,O']-tellurate cures experimental visceral leishmaniasis by redox modulation of Leishmania donovani trypanothione reductase and inhibiting host integrin linked PI3K/Akt pathway.Cellular and molecular life sciences : CMLS · 2018Article
- Changes in the Biophysical Properties of the Cell Membrane Are Involved in the Response ofFrontiers in physiology · 2018Article
- Different apoptosis pathways inCell death discovery · 2018Article
- Methionine aminopeptidase 2 is a key regulator of apoptotic like cell death in Leishmania donovani.Scientific reports · 2017Article
- Observational
- Intracellular zinc flux causes reactive oxygen species mediated mitochondrial dysfunction leading to cell death in Leishmania donovani.PloS one · 2017Article
- AsteraceaeEvidence-based complementary and alternative medicine : eCAM · 2016Article
- Article
- Enzyme Activity Assays for Protein Kinases: Strategies to Identify Active Substrates.Current drug discovery technologies · 2016Review
- Implication of different domains of the Leishmania major metacaspase in cell death and autophagy.Cell death & disease · 2015Article
- Pharmacological assessment defines Leishmania donovani casein kinase 1 as a drug target and reveals important functions in parasite viability and intracellular infection.Antimicrobial agents and chemotherapy · 2014Article
- The calpain inhibitor MDL28170 induces the expression of apoptotic markers in Leishmania amazonensis promastigotes.PloS one · 2014Article
- Alkyl galactofuranosides strongly interact with Leishmania donovani membrane and provide antileishmanial activity.Antimicrobial agents and chemotherapy · 2014Article
- Article
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7 authors at 3 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
The protozoan parasite Leishmania donovani undergoes several developmental transitions in its insect and vertebrate hosts that are induced by environmental changes. The roles of protein kinases in these adaptive differentiation steps and their potential as targets for antiparasitic intervention are only poorly characterized. Here, we used the generic protein kinase inhibitor staurosporine to gain insight into how interference with phosphotransferase activities affects the viability, growth, and motility of L. donovani promastigotes in vitro. Unlike the nonkinase drugs miltefosine and amphotericin B, staurosporine strongly reduced parasite biosynthetic activity and had a cytostatic rather than a cytotoxic effect. Despite the induction of a number of classical apoptotic markers, including caspase-like activity and surface binding of annexin V, we determined that, on the basis of cellular integrity, staurosporine did not cause cell death but caused cell cycle arrest and abrogated parasite motility. In contrast, targeted inhibition of the parasite casein kinase 1 (CK1) protein family by use of the CK1-specific inhibitor D4476 resulted in cell death. Thus, pleiotropic inhibition of L. donovani protein kinases and possibly other ATP-binding proteins by staurosporine dissociates apoptotic marker expression from cell death, which underscores the relevance of specific rather than broad kinase inhibitors for antiparasitic drug development.
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