Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/10194
Title: A putative role for inosine 5′ monophosphate dehydrogenase (IMPDH) in Leishmania amazonensis programmed cell death
Authors: Pitaluga, A. N
Moreira, M. E. C
Traub-Csekö, Y. M
Affilliation: Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular de Parasitas e Vetores. Rio de Janeiro, RJ, Brasil.
Instituto Nacional de Câncer. Divisão de Medicina Experimental. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular de Parasitas e Vetores. Rio de Janeiro, RJ, Brasil.
Abstract: Leishmania amazonensis undergoes apoptosis-like programmed cell death (PCD) under heat shock conditions. We identified a potential role for inosine 5′ monophosphate dehydrogenase (IMPDH) in L. amazonensis PCD. Trypanosomatids do not have a “de novo” purine synthesis pathway, relying on the salvage pathway for survival. IMPDH, a key enzyme in the purine nucleotide pathway, is related to cell growth and apoptosis. Since guanine nucleotide depletion triggers cell cycle arrest and apoptosis in several organisms we analyzed the correlation between IMPDH and apoptosis-like death in L. amazonensis. The L. amazonensis IMPDH inhibition effect on PCD was evaluated through gene expression analysis, mitochondrial depolarization and detection of Annexin-V labeled parasites. We demonstrated a down-regulation of impdh expression under heat shock treatment, which mimics the natural mammalian host infection. Also, IMPDH inhibitors ribavirin and mycophenolic acid (MPA) prevented cell growth and generated an apoptosis-like phenotype in sub-populations of L. amazonensis promastigotes. Our results are in accordance with previous results showing that a subpopulation of parasites undergoes apoptosis-like cell death in the nutrient poor environment of the vector gut. Here, we suggest the involvement of purine metabolism in previously observed apoptosis-like cell death during Leishmania infection.
Keywords: Leishmania amazonensis
IMPDH
Ribavirin
Mycophenolic acid (MPA)
Apoptosis-like programmed cell death
Keywords in spanish: Leishmania
Ribavirina
Apoptosis
keywords: Leishmania
Ribavirina
Apoptose
DeCS: Lieshmania
Ribavirina
Apoptose
Issue Date: 2015
Publisher: Elsevier
Citation: PITALUGA, A.N.; MOREIRA, M.E.C.; TRAUB-CSEKÖ, Y.M. A putative role for inosine 5′ monophosphate dehydrogenase (IMPDH) in Leishmania amazonensis programmed cell death. Experimental Parasitology, v. 149, p. 32-38, 2015.
DOI: 10.1016/j.exppara.2014.12.006
ISSN: 00144894
Embargo date: Fev. 2016
Copyright: restricted access
Appears in Collections:IOC - Artigos de Periódicos

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