DOI . ORG {}
Title[redir]:
Zinc depletion promotes apoptosis-like death in drug-sensitive and antimony-resistance Leishmania donovani | Scientific Reports
Description:
Micronutrients are essential for survival and growth for all the organisms including pathogens. In this manuscript, we report that zinc (Zn) chelator N,N,Nโ,Nโ-tetrakis(2-pyridinylmethyl)-1,2-ethylenediamine (TPEN) affects growth and viability of intracellular pathogen Leishmania donovani (LD) by a concentration and time dependent manner. Simultaneous addition of zinc salt reverses the effect of TPEN. Further experiments provide evidence of apoptosis-like death of the parasite due to Zn-depletion. TPEN treatment enhances caspase-like activity suggesting increase in apoptosis-like events in LD. Specific inhibitors of cathepsin B and Endoclease G block TPEN-induced leishmanial death. Evidences show involvement of reactive oxygen species (ROS) potentially of extra-mitochondrial origin in TPEN-induced LD death. Pentavalent antimonials remained the prime source of treatment against leishmaniasis for several decades; however, antimony-resistant Leishmania is now common source of the disease. We also reveal that Zn-depletion can promote apoptosis-like death in antimony-resistant parasites. In summary, we present a new finding about the role of zinc in the survival of drug sensitive and antimony-resistant LD.
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Keywords {๐}
death, tpen, zinc, pubmed, article, google, scholar, cell, leishmania, cas, treatment, ros, fig, parasites, mitochondrial, generation, apoptosis, assay, cells, role, results, experiments, viability, detected, dna, depletion, activity, central, apoptosislike, growth, donovani, zndepletion, performed, fluorescence, fragmentation, resistant, tunel, nature, parasite, treated, induced, min, presence, independent, antimonyresistant, added, membrane, survival, increase, iron,
Topics {โ๏ธ}
nature portfolio topoisomerase research nature author information authors reprints fresh m199 media 10โยตm tpenโ+โz-vad-fmk carl zeiss-axio-vision-4 m199 media potassium-antimony-tartarate resistant zn-depletion promotes caspase antimony-resistance leishmania donovani zn-depletion induced death mitochondrial protein released mitochondrial membrane depolarisation open zinc depletion-induced death author correspondence original author z-vad-fmk tpen-induced ld death induce ros generation mitochondrial ros generation mitochondrial membrane potential antimony-resistant ld strains caspase-independent dna degradation mitochondrial membrane depolarization trail-mediated apoptosis caspase-independent mitochondrial toxicity estimate ros generation iron enhances generation insulin induced activation ros-sensitive dcf-fluorescence ice-cold 1x pbs antimony-generated stress mitochondrial depolarization leading mitochondria-specific probe jc-1 zinc depletion induces references alam leishmania donovani promastigotes metalloid-induced death increase ros generation mitosox red reagent assessing dna fragmentation confirm dna fragmentation promote dna fragmentation chelate ferrous iron published maps detect ros level fluozin-3am sensitivity
Questions {โ}
- Cell death in Leishmania induced by stress and differentiation: programmed cell death or necrosis?
- Cell death in parasitic protozoa: regulated or incidental?
- Programmed cell death in unicellular parasites: A prerequisite for sustained infection?
- Visceral leishmaniasis: what are the needs for diagnosis, treatment and control?
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headline:Zinc depletion promotes apoptosis-like death in drug-sensitive and antimony-resistance Leishmania donovani
description:Micronutrients are essential for survival and growth for all the organisms including pathogens. In this manuscript, we report that zinc (Zn) chelator N,N,Nรขยย,Nรขยย-tetrakis(2-pyridinylmethyl)-1,2-ethylenediamine (TPEN) affects growth and viability of intracellular pathogen Leishmania donovani (LD) by a concentration and time dependent manner. Simultaneous addition of zinc salt reverses the effect of TPEN. Further experiments provide evidence of apoptosis-like death of the parasite due to Zn-depletion. TPEN treatment enhances caspase-like activity suggesting increase in apoptosis-like events in LD. Specific inhibitors of cathepsin B and Endoclease G block TPEN-induced leishmanial death. Evidences show involvement of reactive oxygen species (ROS) potentially of extra-mitochondrial origin in TPEN-induced LD death. Pentavalent antimonials remained the prime source of treatment against leishmaniasis for several decades; however, antimony-resistant Leishmania is now common source of the disease. We also reveal that Zn-depletion can promote apoptosis-like death in antimony-resistant parasites. In summary, we present a new finding about the role of zinc in the survival of drug sensitive and antimony-resistant LD.
datePublished:2017-09-05T00:00:00Z
dateModified:2017-09-05T00:00:00Z
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headline:Zinc depletion promotes apoptosis-like death in drug-sensitive and antimony-resistance Leishmania donovani
description:Micronutrients are essential for survival and growth for all the organisms including pathogens. In this manuscript, we report that zinc (Zn) chelator N,N,Nรขยย,Nรขยย-tetrakis(2-pyridinylmethyl)-1,2-ethylenediamine (TPEN) affects growth and viability of intracellular pathogen Leishmania donovani (LD) by a concentration and time dependent manner. Simultaneous addition of zinc salt reverses the effect of TPEN. Further experiments provide evidence of apoptosis-like death of the parasite due to Zn-depletion. TPEN treatment enhances caspase-like activity suggesting increase in apoptosis-like events in LD. Specific inhibitors of cathepsin B and Endoclease G block TPEN-induced leishmanial death. Evidences show involvement of reactive oxygen species (ROS) potentially of extra-mitochondrial origin in TPEN-induced LD death. Pentavalent antimonials remained the prime source of treatment against leishmaniasis for several decades; however, antimony-resistant Leishmania is now common source of the disease. We also reveal that Zn-depletion can promote apoptosis-like death in antimony-resistant parasites. In summary, we present a new finding about the role of zinc in the survival of drug sensitive and antimony-resistant LD.
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