DOI . ORG {}
Title[redir]:
Methionine aminopeptidase 2 is a key regulator of apoptotic like cell death in Leishmania donovani | Scientific Reports
Description:
We investigate the role of methionine aminopeptidase 2 (MAP2) in miltefosine induced programmed cell death (PCD) in promastigote form of L. donovani. We report that TNP-470, an inhibitor of MAP2, inhibits programmed cell death in miltefosine treated promastigotes. It inhibits the biochemical features of metazoan apoptosis, including caspase3/7 protease like activity, oligonucleosomal DNA fragmentation, collapse of mitochondrial transmembrane potential, and increase in cytosolic pool of calcium ions but did not prevent the cell death and phosphatidyl serine externalization. The data suggests that the MAP2 is involved in the regulation of PCD in parasite. Moreover, TNP-470 shows the leishmanicidal activity (IC50 = 15 µM) and in vitro inhibition of LdMAP2 activity (K i = 13.5 nM). Further studies on MAP2 and identification of death signaling pathways provide valuable information that could be exploited to understand the role of non caspase proteases in PCD of L. donovani.
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Keywords {🔍}
cells, cell, miltefosine, pubmed, treated, article, tnp, cas, google, scholar, death, leishmania, donovani, promastigotes, map, apoptosis, activity, dna, ldmap, apoptotic, induced, caspase, fig, promastigote, control, fragmentation, nature, protease, parasite, inhibitor, inhibition, role, reported, analysis, methionine, assay, fluorescence, increase, protein, dubey, pcd, membrane, genomic, buffer, showed, kumar, concentration, dmso, potential, calcium,
Topics {✒️}
n-acetyl-asp-glu-val-asp-al nature portfolio author information authors research funding nature references das m199 media supplemented 0/ reprints author correspondence generate pet-28a-ldmap2 plasmid development alpha-acetyl transferase families ar-kr laser beam bt/555/ne/u-excel/2014 boc-d-fmk prevent steady-state kinetic characterization ni-nta affinity chromatography n-terminal methionine residue amino-terminal methionine processing confocal microscopy data caspase-independent mitochondrial toxicity vikash kumar dubey metal-substituted methionine aminopeptidase annexin v-fitc binds 50 mm tris-hcl buffer vitro betulin-induced apoptosis hypericin-induced parasite death media india miltefosine-unresponsive leishmania donovani broad spectrum calpain staurosporine-treated leishmania donovani calpain/cysteine protease inhibitors flow cytometric analysis ne laser beam s2 rights ni-nta purified ldmap2 facscalibur flow cytometer article kumar reactive oxygen species annexin v-fitc annexin-v-fitc pre-incubated reaction mixture caspase specific inhibitors17 anti leishmaniasis activity n-terminal processing leishmania results map2 inhibitors prevents lineweaver-burk plots lower membrane potential
Questions {❓}
- Cell death in Leishmania induced by stress and differentiation: programmed cell death or necrosis?
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WebPage:
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headline:Methionine aminopeptidase 2 is a key regulator of apoptotic like cell death in Leishmania donovani
description:We investigate the role of methionine aminopeptidase 2 (MAP2) in miltefosine induced programmed cell death (PCD) in promastigote form of L. donovani. We report that TNP-470, an inhibitor of MAP2, inhibits programmed cell death in miltefosine treated promastigotes. It inhibits the biochemical features of metazoan apoptosis, including caspase3/7 protease like activity, oligonucleosomal DNA fragmentation, collapse of mitochondrial transmembrane potential, and increase in cytosolic pool of calcium ions but did not prevent the cell death and phosphatidyl serine externalization. The data suggests that the MAP2 is involved in the regulation of PCD in parasite. Moreover, TNP-470 shows the leishmanicidal activity (IC50â=â15âµM) and in vitro inhibition of LdMAP2 activity (K
i
â=â13.5ânM). Further studies on MAP2 and identification of death signaling pathways provide valuable information that could be exploited to understand the role of non caspase proteases in PCD of L. donovani.
datePublished:2017-03-07T00:00:00Z
dateModified:2017-03-07T00:00:00Z
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Hydrolases
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headline:Methionine aminopeptidase 2 is a key regulator of apoptotic like cell death in Leishmania donovani
description:We investigate the role of methionine aminopeptidase 2 (MAP2) in miltefosine induced programmed cell death (PCD) in promastigote form of L. donovani. We report that TNP-470, an inhibitor of MAP2, inhibits programmed cell death in miltefosine treated promastigotes. It inhibits the biochemical features of metazoan apoptosis, including caspase3/7 protease like activity, oligonucleosomal DNA fragmentation, collapse of mitochondrial transmembrane potential, and increase in cytosolic pool of calcium ions but did not prevent the cell death and phosphatidyl serine externalization. The data suggests that the MAP2 is involved in the regulation of PCD in parasite. Moreover, TNP-470 shows the leishmanicidal activity (IC50â=â15âµM) and in vitro inhibition of LdMAP2 activity (K
i
â=â13.5ânM). Further studies on MAP2 and identification of death signaling pathways provide valuable information that could be exploited to understand the role of non caspase proteases in PCD of L. donovani.
datePublished:2017-03-07T00:00:00Z
dateModified:2017-03-07T00:00:00Z
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