1,4-Diamino-2-butanone, a wide-spectrum microbicide, yields reactive species by metal-catalyzed oxidation
Autor(a) principal: | |
---|---|
Data de Publicação: | 2011 |
Outros Autores: | , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNIFESP |
Texto Completo: | http://repositorio.unifesp.br/handle/11600/33801 http://dx.doi.org/10.1016/j.freeradbiomed.2011.03.033 |
Resumo: | 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. |
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Soares, Chrislaine OliveiraAlves, Maria Julia MansoBechara, Etelvino José Henriques [UNIFESP]Universidade de São Paulo (USP)Universidade Federal de São Paulo (UNIFESP)2016-01-24T14:16:53Z2016-01-24T14:16:53Z2011-06-15Free Radical Biology and Medicine. New York: Elsevier B.V., v. 50, n. 12, p. 1760-1770, 2011.0891-5849http://repositorio.unifesp.br/handle/11600/33801http://dx.doi.org/10.1016/j.freeradbiomed.2011.03.033WOS000291233200006.pdf10.1016/j.freeradbiomed.2011.03.033WOS:000291233200006The 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.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)INCT Processos Redox em Biomedicina-RedoxomaUniv São Paulo, Inst Quim, Dept Bioquim, BR-05508900 São Paulo, BrazilUniversidade Federal de São Paulo, Inst Ciencias Ambientais Quim & Farmaceut, Dept Ciencias Exatas & Terra, Diadema, SP, BrazilUniversidade Federal de São Paulo, Inst Ciencias Ambientais Quim & Farmaceut, Dept Ciencias Exatas & Terra, Diadema, SP, BrazilWeb of Science1760-1770engElsevier B.V.Free Radical Biology and Medicinehttp://www.elsevier.com/about/open-access/open-access-policies/article-posting-policyinfo:eu-repo/semantics/openAccess1,4-Diamino-2-butanonealpha-Aminoketonesalpha-OxoaldehydesReactive oxygen speciesFerritinTransferrinOxidative damageFree radicals1,4-Diamino-2-butanone, a wide-spectrum microbicide, yields reactive species by metal-catalyzed oxidationinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlereponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESPORIGINALWOS000291233200006.pdfapplication/pdf1440993${dspace.ui.url}/bitstream/11600/33801/1/WOS000291233200006.pdfc93c02c0cbe1a98bd010f8d0f65c046bMD51open accessTEXTWOS000291233200006.pdf.txtWOS000291233200006.pdf.txtExtracted texttext/plain48823${dspace.ui.url}/bitstream/11600/33801/9/WOS000291233200006.pdf.txtcc6eead696bae358072b3f670ab11978MD59open accessTHUMBNAILWOS000291233200006.pdf.jpgWOS000291233200006.pdf.jpgIM Thumbnailimage/jpeg7910${dspace.ui.url}/bitstream/11600/33801/11/WOS000291233200006.pdf.jpg95419b735e16877d52335827a88e2c2bMD511open access11600/338012023-06-05 19:22:11.699open accessoai:repositorio.unifesp.br:11600/33801Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestopendoar:34652023-06-05T22:22:11Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false |
dc.title.en.fl_str_mv |
1,4-Diamino-2-butanone, a wide-spectrum microbicide, yields reactive species by metal-catalyzed oxidation |
title |
1,4-Diamino-2-butanone, a wide-spectrum microbicide, yields reactive species by metal-catalyzed oxidation |
spellingShingle |
1,4-Diamino-2-butanone, a wide-spectrum microbicide, yields reactive species by metal-catalyzed oxidation Soares, Chrislaine Oliveira 1,4-Diamino-2-butanone alpha-Aminoketones alpha-Oxoaldehydes Reactive oxygen species Ferritin Transferrin Oxidative damage Free radicals |
title_short |
1,4-Diamino-2-butanone, a wide-spectrum microbicide, yields reactive species by metal-catalyzed oxidation |
title_full |
1,4-Diamino-2-butanone, a wide-spectrum microbicide, yields reactive species by metal-catalyzed oxidation |
title_fullStr |
1,4-Diamino-2-butanone, a wide-spectrum microbicide, yields reactive species by metal-catalyzed oxidation |
title_full_unstemmed |
1,4-Diamino-2-butanone, a wide-spectrum microbicide, yields reactive species by metal-catalyzed oxidation |
title_sort |
1,4-Diamino-2-butanone, a wide-spectrum microbicide, yields reactive species by metal-catalyzed oxidation |
author |
Soares, Chrislaine Oliveira |
author_facet |
Soares, Chrislaine Oliveira Alves, Maria Julia Manso Bechara, Etelvino José Henriques [UNIFESP] |
author_role |
author |
author2 |
Alves, Maria Julia Manso Bechara, Etelvino José Henriques [UNIFESP] |
author2_role |
author author |
dc.contributor.institution.none.fl_str_mv |
Universidade de São Paulo (USP) Universidade Federal de São Paulo (UNIFESP) |
dc.contributor.author.fl_str_mv |
Soares, Chrislaine Oliveira Alves, Maria Julia Manso Bechara, Etelvino José Henriques [UNIFESP] |
dc.subject.eng.fl_str_mv |
1,4-Diamino-2-butanone alpha-Aminoketones alpha-Oxoaldehydes Reactive oxygen species Ferritin Transferrin Oxidative damage Free radicals |
topic |
1,4-Diamino-2-butanone alpha-Aminoketones alpha-Oxoaldehydes Reactive oxygen species Ferritin Transferrin Oxidative damage Free radicals |
description |
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. |
publishDate |
2011 |
dc.date.issued.fl_str_mv |
2011-06-15 |
dc.date.accessioned.fl_str_mv |
2016-01-24T14:16:53Z |
dc.date.available.fl_str_mv |
2016-01-24T14:16:53Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
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article |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
Free Radical Biology and Medicine. New York: Elsevier B.V., v. 50, n. 12, p. 1760-1770, 2011. |
dc.identifier.uri.fl_str_mv |
http://repositorio.unifesp.br/handle/11600/33801 http://dx.doi.org/10.1016/j.freeradbiomed.2011.03.033 |
dc.identifier.issn.none.fl_str_mv |
0891-5849 |
dc.identifier.file.none.fl_str_mv |
WOS000291233200006.pdf |
dc.identifier.doi.none.fl_str_mv |
10.1016/j.freeradbiomed.2011.03.033 |
dc.identifier.wos.none.fl_str_mv |
WOS:000291233200006 |
identifier_str_mv |
Free Radical Biology and Medicine. New York: Elsevier B.V., v. 50, n. 12, p. 1760-1770, 2011. 0891-5849 WOS000291233200006.pdf 10.1016/j.freeradbiomed.2011.03.033 WOS:000291233200006 |
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http://repositorio.unifesp.br/handle/11600/33801 http://dx.doi.org/10.1016/j.freeradbiomed.2011.03.033 |
dc.language.iso.fl_str_mv |
eng |
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eng |
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Free Radical Biology and Medicine |
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http://www.elsevier.com/about/open-access/open-access-policies/article-posting-policy |
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openAccess |
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1760-1770 |
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Elsevier B.V. |
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Elsevier B.V. |
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