1,4-Diamino-2-butanone, a putrescine analogue, promotes redox imbalance in Trypanosoma cruzi and mammalian cells

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dc.contributor.authorSoares, Chrislaine O
dc.contributor.authorColli, Walter
dc.contributor.authorBechara, Etelvino José Henriques [UNIFESP]
dc.contributor.authorAlves, Maria Julia Manso
dc.contributor.institutionUniversidade de São Paulo (USP)
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.date.accessioned2016-01-24T14:28:09Z
dc.date.available2016-01-24T14:28:09Z
dc.date.issued2012-12-15
dc.description.abstractThe putrescine analogue 1,4-diamino-2-butanone (DAB) is highly toxic to various microorganisms, including Trypanosoma cruzi. Similar to other a-aminocarbonyl metabolites. DAB exhibits pro-oxidant properties. DAB undergoes metal-catalyzed oxidation yielding H2O2, NH4+ ion, and a highly toxic alpha-oxoaldehyde. in vitro. DAB decreases mammalian cell viability associated with changes in redox balance. Here, we aim to clarify the DAB pro-oxidant effects on trypomastigotes and on intracellular T. cruzi amastigotes. DAB (0.05-5 mM) exposure in trypomastigotes, the infective stage of T. cruzi, leads to a decline in parasite viability (IC50 c.a. 0.2 mM DAB; 4 h incubation), changes in morphology, thiol redox imbalance, and increased TcSOD activity. Medium supplementation with catalase (2.5 mu M) protects trypomastigotes against DAB toxicity, while host cell invasion by trypomastigotes is hampered by DAB. Additionally, intracellular amastigotes are susceptible to DAB toxicity. Furthermore, pre-treatment with 100-500 mu M buthionine sulfoximine (BSO) of LLC-MK2 potentiates DAB cytotoxicity, whereas 5 mM N-acetyl-cysteine (NAC) protects cells from oxidative stress. Together, these data support the hypothesis that redox imbalance contributes to DAB cytotoxicity in both T. cruzi and mammalian host cells. (C) 2012 Elsevier Inc. All rights reserved.en
dc.description.affiliationUniv São Paulo, Inst Quim, Dept Bioquim, BR-01498 São Paulo, Brazil
dc.description.affiliationUniversidade Federal de São Paulo, Inst Ciencias Ambientais Quim & Farmaceut, Dept Ciencias Exatas & Terra, Diadema, SP, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Inst Ciencias Ambientais Quim & Farmaceut, Dept Ciencias Exatas & Terra, Diadema, SP, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.description.sponsorshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.description.sponsorshipINCT Processos Redox em Biomedicina - Redoxoma
dc.format.extent103-110
dc.identifierhttp://dx.doi.org/10.1016/j.abb.2012.09.005
dc.identifier.citationArchives of Biochemistry and Biophysics. New York: Elsevier B.V., v. 528, n. 2, p. 103-110, 2012.
dc.identifier.doi10.1016/j.abb.2012.09.005
dc.identifier.fileWOS000312236700001.pdf
dc.identifier.issn0003-9861
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/35614
dc.identifier.wosWOS:000312236700001
dc.language.isoeng
dc.publisherElsevier B.V.
dc.relation.ispartofArchives of Biochemistry and Biophysics
dc.rightsAcesso aberto
dc.rights.licensehttp://www.elsevier.com/about/open-access/open-access-policies/article-posting-policy
dc.subject1,4-Diamino-2-butanoneen
dc.subjectPolyamineen
dc.subjectalpha-Oxoaldehydeen
dc.subjectTrypanosoma cruzien
dc.subjectLLC-MK2 cellen
dc.subjectRedox imbalanceen
dc.title1,4-Diamino-2-butanone, a putrescine analogue, promotes redox imbalance in Trypanosoma cruzi and mammalian cellsen
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