Methionine aminopeptidase 2 is a key regulator of apoptotic like cell death in Leishmania donovani

Abstract 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 biochemica...

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Autores principales:	Ritesh Kumar, Kartikeya Tiwari, Vikash Kumar Dubey
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/eae507987eb945d5a3481885f159af9c
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spelling	oai:doaj.org-article:eae507987eb945d5a3481885f159af9c2021-12-02T15:04:55ZMethionine aminopeptidase 2 is a key regulator of apoptotic like cell death in Leishmania donovani10.1038/s41598-017-00186-92045-2322https://doaj.org/article/eae507987eb945d5a3481885f159af9c2017-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-00186-9https://doaj.org/toc/2045-2322Abstract 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.Ritesh KumarKartikeya TiwariVikash Kumar DubeyNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ritesh Kumar Kartikeya Tiwari Vikash Kumar Dubey Methionine aminopeptidase 2 is a key regulator of apoptotic like cell death in Leishmania donovani
description	Abstract 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.
format	article
author	Ritesh Kumar Kartikeya Tiwari Vikash Kumar Dubey
author_facet	Ritesh Kumar Kartikeya Tiwari Vikash Kumar Dubey
author_sort	Ritesh Kumar
title	Methionine aminopeptidase 2 is a key regulator of apoptotic like cell death in Leishmania donovani
title_short	Methionine aminopeptidase 2 is a key regulator of apoptotic like cell death in Leishmania donovani
title_full	Methionine aminopeptidase 2 is a key regulator of apoptotic like cell death in Leishmania donovani
title_fullStr	Methionine aminopeptidase 2 is a key regulator of apoptotic like cell death in Leishmania donovani
title_full_unstemmed	Methionine aminopeptidase 2 is a key regulator of apoptotic like cell death in Leishmania donovani
title_sort	methionine aminopeptidase 2 is a key regulator of apoptotic like cell death in leishmania donovani
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/eae507987eb945d5a3481885f159af9c
work_keys_str_mv	AT riteshkumar methionineaminopeptidase2isakeyregulatorofapoptoticlikecelldeathinleishmaniadonovani AT kartikeyatiwari methionineaminopeptidase2isakeyregulatorofapoptoticlikecelldeathinleishmaniadonovani AT vikashkumardubey methionineaminopeptidase2isakeyregulatorofapoptoticlikecelldeathinleishmaniadonovani
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Methionine aminopeptidase 2 is a key regulator of apoptotic like cell death in Leishmania donovani

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