1,4-Diamino-2-butanone, a wide-spectrum microbicide, yields reactive species by metal-catalyzed oxidation

Mostrar registro simples

dc.contributor.author Soares, Chrislaine Oliveira
dc.contributor.author Alves, Maria Julia Manso
dc.contributor.author Bechara, Etelvino José Henriques [UNIFESP]
dc.date.accessioned 2016-01-24T14:16:53Z
dc.date.available 2016-01-24T14:16:53Z
dc.date.issued 2011-06-15
dc.identifier http://dx.doi.org/10.1016/j.freeradbiomed.2011.03.033
dc.identifier.citation Free Radical Biology and Medicine. New York: Elsevier B.V., v. 50, n. 12, p. 1760-1770, 2011.
dc.identifier.issn 0891-5849
dc.identifier.uri http://repositorio.unifesp.br/handle/11600/33801
dc.description.abstract The alpha-aminoketone 1,4-diamino-2-butanone (DAB), a putrescine analogue, is highly toxic to various microorganisms, including Trypanosoma cruzi. However, little is known about the molecular mechanisms underlying DAB's cytotoxic properties. We report here that DAB (pK(a) 7.5 and 9.5) undergoes aerobic oxidation in phosphate buffer, pH 7.4, at 37 degrees C, catalyzed by Fe(II) and Cu(II) ions yielding NH(4)(+) ion, H(2)O(2), and 4-amino-2-oxobutanal (oxoDAB). OxoDAB, like methylglyoxal and other alpha-oxoaldehydes, is expected to cause protein aggregation and nucleobase lesions. Propagation of DAB oxidation by superoxide radical was confirmed by the inhibitory effect of added SOD (50 U ml(-1)) and stimulatory effect of xanthine/xanthine oxidase, a source of superoxide radical. EPR spin trapping studies with 5,5-dimethyl-1-pyrroline-1-oxide (DMPO) revealed an adduct attributable to DMPO-HO(center dot), and those with alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone or 3,5-dibromo-4-nitrosobenzenesulfonic acid, a six-line adduct assignable to a DAB(center dot) resonant enoyl radical adduct. Added horse spleen ferritin (HoSF) and bovine apo-transferrin underwent oxidative changes in tryptophan residues in the presence of 1.0-10 mM DAB. Iron release from HoSF was observed as well. Assays performed with fluorescein-encapsulated liposomes of cardiolipin and phosphatidylcholine (20:80) incubated with DAB resulted in extensive lipid peroxidation and consequent vesicle permeabilization. DAB (0-10 mM) administration to cultured LLC-MK2 epithelial cells caused a decline in cell viability, which was inhibited by preaddition of either catalase (4.5 mu M) or aminoguanidine (25 mM). Our findings support the hypothesis that DAB toxicity to several pathogenic microorganisms previously described may involve not only reported inhibition of polyamine metabolism but also DAB pro-oxidant activity. (C) 2011 Elsevier Inc. All rights reserved. en
dc.description.sponsorship Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorship Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.description.sponsorship Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.description.sponsorship INCT Processos Redox em Biomedicina-Redoxoma
dc.format.extent 1760-1770
dc.language.iso eng
dc.publisher Elsevier B.V.
dc.relation.ispartof Free Radical Biology and Medicine
dc.rights Acesso aberto
dc.subject 1,4-Diamino-2-butanone en
dc.subject alpha-Aminoketones en
dc.subject alpha-Oxoaldehydes en
dc.subject Reactive oxygen species en
dc.subject Ferritin en
dc.subject Transferrin en
dc.subject Oxidative damage en
dc.subject Free radicals en
dc.title 1,4-Diamino-2-butanone, a wide-spectrum microbicide, yields reactive species by metal-catalyzed oxidation en
dc.type Artigo
dc.rights.license http://www.elsevier.com/about/open-access/open-access-policies/article-posting-policy
dc.contributor.institution Universidade de São Paulo (USP)
dc.contributor.institution Universidade Federal de São Paulo (UNIFESP)
dc.description.affiliation Univ São Paulo, Inst Quim, Dept Bioquim, BR-05508900 São Paulo, Brazil
dc.description.affiliation Universidade Federal de São Paulo, Inst Ciencias Ambientais Quim & Farmaceut, Dept Ciencias Exatas & Terra, Diadema, SP, Brazil
dc.description.affiliationUnifesp Universidade Federal de São Paulo, Inst Ciencias Ambientais Quim & Farmaceut, Dept Ciencias Exatas & Terra, Diadema, SP, Brazil
dc.identifier.file WOS000291233200006.pdf
dc.identifier.doi 10.1016/j.freeradbiomed.2011.03.033
dc.description.source Web of Science
dc.identifier.wos WOS:000291233200006



Arquivos deste item

Nome: WOS000291233200006.pdf
Tamanho: 1.440Mb
Formato: PDF
Descrição:
Visualizar/Abrir

Este item aparece na(s) seguinte(s) coleção(s)

Mostrar registro simples