The putrescine analogue 1,4-diamino-2-butanone affects polyamine synthesis, transport, ultrastructure and intracellular survival in Leishmania amazonensis

Detalhes bibliográficos
Autor(a) principal: Santos, Marcos André Vannier dos
Data de Publicação: 2008
Outros Autores: Menezes, Diego Silva, Oliveira, Marcus Fernandes de, Mello, Fernando G. de
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/1962
Resumo: Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil
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spelling Santos, Marcos André Vannier dosMenezes, Diego SilvaOliveira, Marcus Fernandes deMello, Fernando G. de2011-04-25T19:30:40Z2011-04-25T19:30:40Z2008VANNIER-SANTOS, M. A. et al. The putrescine analogue 1,4-diamino-2-butanone affects polyamine synthesis, transport, ultrastructure and intracellular survival in Leishmania amazonensis. Microbiology, v. 154, n.10, p. 3104-3111. Oct. 2008.1350-0872https://www.arca.fiocruz.br/handle/icict/196210.1099/mic.0.2007/013896-0engThe putrescine analogue 1,4-diamino-2-butanone affects polyamine synthesis, transport, ultrastructure and intracellular survival in Leishmania amazonensisinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilUniversidade Federal do Rio de Janeiro. Instituto de Bioquımica Medica. Rio de Janeiro, RJ, BrasilUniversidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, BrasilPolyamines are important regulators of growth and differentiation in a variety of cells, including parasitic protozoa. Promastigotes of Leishmania species have high levels of putrescine and spermidine and their growth can be inhibited by polyamine biosynthesis antagonists. The putrescine analogue 1,4-diamino-2-butanone (DAB) is microbicidal against Tritrichomonas foetus and Trypanosoma cruzi, so we tested its effects on Leishmania amazonensis proliferation, viability, organization, putrescine transport and synthesis as well as in vitro infectivity. DAB impaired promastigote proliferation dose-dependently (IC(50) 144 microM) and the parasite putrescine concentration was reduced by nearly 50 %. This analogue markedly inhibited both ornithine decarboxylase activity and [H(3)]putrescine uptake by promastigotes. Pre-treatment with DAB for 24 h led to compensatory enhancement of putrescine uptake, indicating an adaptive mechanism in DAB-treated parasites. Remarkably, DAB caused mitochondrial damage, assessed by transmission electron microscopy, and 3 h treatment with 1 mM DAB enhanced lipid peroxidation, whereas incubation with 10 mM DAB or for 24 h resulted in decreased peroxidation levels in the parasites. This effect was probably due to the loss of mitochondrial function, demonstrated by the diminished reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), not observed in macrophages. Murine macrophages infected with L. amazonensis amastigotes treated with DAB had parasite loads significantly (P<0.05) lower than controls, presumably due to interference with putrescine uptake and/or synthesis. These results suggest that putrescine may be involved in leishmanial survival, possibly by maintaining the parasite's mitochondrial function. The use of analogues to interfere with polyamine/diamine synthesis and transport may shed light on its function in intracellular parasite survival and lead to identification of new targets for leishmaniasis chemotherapy.PutrescinaPoliaminasMicroscopia Eletrônica de TransmissãoLeishmaniaAntiprotozoáriosMitocôndriasCamundongosMacrófagosinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZORIGINALThe putrescine analogue 1,4-diamino-2-butanone.pdfThe putrescine analogue 1,4-diamino-2-butanone.pdfapplication/pdf238191https://www.arca.fiocruz.br/bitstream/icict/1962/1/The%20putrescine%20analogue%201%2c4-diamino-2-butanone.pdf76b216fb35e79e44266fb1a72ae2b66fMD51LICENSElicense.txtlicense.txttext/plain; charset=utf-81648https://www.arca.fiocruz.br/bitstream/icict/1962/2/license.txte095249ac7cacefbfe39684dfe45e706MD52TEXTThe putrescine analogue 1,4-diamino-2-butanone.pdf.txtThe putrescine analogue 1,4-diamino-2-butanone.pdf.txtExtracted texttext/plain42684https://www.arca.fiocruz.br/bitstream/icict/1962/5/The%20putrescine%20analogue%201%2c4-diamino-2-butanone.pdf.txt5c69772b615ddc69e00bd66b69462018MD55THUMBNAILThe putrescine analogue 1,4-diamino-2-butanone.pdf.jpgThe putrescine analogue 1,4-diamino-2-butanone.pdf.jpgGenerated Thumbnailimage/jpeg2406https://www.arca.fiocruz.br/bitstream/icict/1962/4/The%20putrescine%20analogue%201%2c4-diamino-2-butanone.pdf.jpg9226e659883466792fd1c952be9f4e46MD54icict/19622023-03-15 14:33:23.879oai:www.arca.fiocruz.br:icict/1962Tk9OLUVYQ0xVU0lWRSBESVNUUklCVVRJT04gTElDRU5TRQoKQnkgc2lnbmluZyBhbmQgc3VibWl0dGluZyB0aGlzIGxpY2Vuc2UsIHlvdSAodGhlIGF1dGhvcihzKSBvciBjb3B5cmlnaHQKb3duZXIpIGdyYW50cyB0byBEU3BhY2UgVW5pdmVyc2l0eSAoRFNVKSB0aGUgbm9uLWV4Y2x1c2l2ZSByaWdodCB0byByZXByb2R1Y2UsCnRyYW5zbGF0ZSAoYXMgZGVmaW5lZCBiZWxvdyksIGFuZC9vciBkaXN0cmlidXRlIHlvdXIgc3VibWlzc2lvbiAoaW5jbHVkaW5nCnRoZSBhYnN0cmFjdCkgd29ybGR3aWRlIGluIHByaW50IGFuZCBlbGVjdHJvbmljIGZvcm1hdCBhbmQgaW4gYW55IG1lZGl1bSwKaW5jbHVkaW5nIGJ1dCBub3QgbGltaXRlZCB0byBhdWRpbyBvciB2aWRlby4KCllvdSBhZ3JlZSB0aGF0IERTVSBtYXksIHdpdGhvdXQgY2hhbmdpbmcgdGhlIGNvbnRlbnQsIHRyYW5zbGF0ZSB0aGUKc3VibWlzc2lvbiB0byBhbnkgbWVkaXVtIG9yIGZvcm1hdCBmb3IgdGhlIHB1cnBvc2Ugb2YgcHJlc2VydmF0aW9uLgoKWW91IGFsc28gYWdyZWUgdGhhdCBEU1UgbWF5IGtlZXAgbW9yZSB0aGFuIG9uZSBjb3B5IG9mIHRoaXMgc3VibWlzc2lvbiBmb3IKcHVycG9zZXMgb2Ygc2VjdXJpdHksIGJhY2stdXAgYW5kIHByZXNlcnZhdGlvbi4KCllvdSByZXByZXNlbnQgdGhhdCB0aGUgc3VibWlzc2lvbiBpcyB5b3VyIG9yaWdpbmFsIHdvcmssIGFuZCB0aGF0IHlvdSBoYXZlCnRoZSByaWdodCB0byBncmFudCB0aGUgcmlnaHRzIGNvbnRhaW5lZCBpbiB0aGlzIGxpY2Vuc2UuIFlvdSBhbHNvIHJlcHJlc2VudAp0aGF0IHlvdXIgc3VibWlzc2lvbiBkb2VzIG5vdCwgdG8gdGhlIGJlc3Qgb2YgeW91ciBrbm93bGVkZ2UsIGluZnJpbmdlIHVwb24KYW55b25lJ3MgY29weXJpZ2h0LgoKSWYgdGhlIHN1Ym1pc3Npb24gY29udGFpbnMgbWF0ZXJpYWwgZm9yIHdoaWNoIHlvdSBkbyBub3QgaG9sZCBjb3B5cmlnaHQsCnlvdSByZXByZXNlbnQgdGhhdCB5b3UgaGF2ZSBvYnRhaW5lZCB0aGUgdW5yZXN0cmljdGVkIHBlcm1pc3Npb24gb2YgdGhlCmNvcHlyaWdodCBvd25lciB0byBncmFudCBEU1UgdGhlIHJpZ2h0cyByZXF1aXJlZCBieSB0aGlzIGxpY2Vuc2UsIGFuZCB0aGF0CnN1Y2ggdGhpcmQtcGFydHkgb3duZWQgbWF0ZXJpYWwgaXMgY2xlYXJseSBpZGVudGlmaWVkIGFuZCBhY2tub3dsZWRnZWQKd2l0aGluIHRoZSB0ZXh0IG9yIGNvbnRlbnQgb2YgdGhlIHN1Ym1pc3Npb24uCgpJRiBUSEUgU1VCTUlTU0lPTiBJUyBCQVNFRCBVUE9OIFdPUksgVEhBVCBIQVMgQkVFTiBTUE9OU09SRUQgT1IgU1VQUE9SVEVECkJZIEFOIEFHRU5DWSBPUiBPUkdBTklaQVRJT04gT1RIRVIgVEhBTiBEU1UsIFlPVSBSRVBSRVNFTlQgVEhBVCBZT1UgSEFWRQpGVUxGSUxMRUQgQU5ZIFJJR0hUIE9GIFJFVklFVyBPUiBPVEhFUiBPQkxJR0FUSU9OUyBSRVFVSVJFRCBCWSBTVUNICkNPTlRSQUNUIE9SIEFHUkVFTUVOVC4KCkRTVSB3aWxsIGNsZWFybHkgaWRlbnRpZnkgeW91ciBuYW1lKHMpIGFzIHRoZSBhdXRob3Iocykgb3Igb3duZXIocykgb2YgdGhlCnN1Ym1pc3Npb24sIGFuZCB3aWxsIG5vdCBtYWtlIGFueSBhbHRlcmF0aW9uLCBvdGhlciB0aGFuIGFzIGFsbG93ZWQgYnkgdGhpcwpsaWNlbnNlLCB0byB5b3VyIHN1Ym1pc3Npb24uCg==Repositório InstitucionalPUBhttps://www.arca.fiocruz.br/oai/requestrepositorio.arca@fiocruz.bropendoar:21352023-03-15T17:33:23Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)false
dc.title.pt_BR.fl_str_mv The putrescine analogue 1,4-diamino-2-butanone affects polyamine synthesis, transport, ultrastructure and intracellular survival in Leishmania amazonensis
title The putrescine analogue 1,4-diamino-2-butanone affects polyamine synthesis, transport, ultrastructure and intracellular survival in Leishmania amazonensis
spellingShingle The putrescine analogue 1,4-diamino-2-butanone affects polyamine synthesis, transport, ultrastructure and intracellular survival in Leishmania amazonensis
Santos, Marcos André Vannier dos
Putrescina
Poliaminas
Microscopia Eletrônica de Transmissão
Leishmania
Antiprotozoários
Mitocôndrias
Camundongos
Macrófagos
title_short The putrescine analogue 1,4-diamino-2-butanone affects polyamine synthesis, transport, ultrastructure and intracellular survival in Leishmania amazonensis
title_full The putrescine analogue 1,4-diamino-2-butanone affects polyamine synthesis, transport, ultrastructure and intracellular survival in Leishmania amazonensis
title_fullStr The putrescine analogue 1,4-diamino-2-butanone affects polyamine synthesis, transport, ultrastructure and intracellular survival in Leishmania amazonensis
title_full_unstemmed The putrescine analogue 1,4-diamino-2-butanone affects polyamine synthesis, transport, ultrastructure and intracellular survival in Leishmania amazonensis
title_sort The putrescine analogue 1,4-diamino-2-butanone affects polyamine synthesis, transport, ultrastructure and intracellular survival in Leishmania amazonensis
author Santos, Marcos André Vannier dos
author_facet Santos, Marcos André Vannier dos
Menezes, Diego Silva
Oliveira, Marcus Fernandes de
Mello, Fernando G. de
author_role author
author2 Menezes, Diego Silva
Oliveira, Marcus Fernandes de
Mello, Fernando G. de
author2_role author
author
author
dc.contributor.author.fl_str_mv Santos, Marcos André Vannier dos
Menezes, Diego Silva
Oliveira, Marcus Fernandes de
Mello, Fernando G. de
dc.subject.decs.pt_BR.fl_str_mv Putrescina
Poliaminas
Microscopia Eletrônica de Transmissão
Leishmania
Antiprotozoários
Mitocôndrias
Camundongos
Macrófagos
topic Putrescina
Poliaminas
Microscopia Eletrônica de Transmissão
Leishmania
Antiprotozoários
Mitocôndrias
Camundongos
Macrófagos
description Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil
publishDate 2008
dc.date.issued.fl_str_mv 2008
dc.date.accessioned.fl_str_mv 2011-04-25T19:30:40Z
dc.date.available.fl_str_mv 2011-04-25T19:30:40Z
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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status_str publishedVersion
dc.identifier.citation.fl_str_mv VANNIER-SANTOS, M. A. et al. The putrescine analogue 1,4-diamino-2-butanone affects polyamine synthesis, transport, ultrastructure and intracellular survival in Leishmania amazonensis. Microbiology, v. 154, n.10, p. 3104-3111. Oct. 2008.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/1962
dc.identifier.issn.none.fl_str_mv 1350-0872
dc.identifier.doi.none.fl_str_mv 10.1099/mic.0.2007/013896-0
identifier_str_mv VANNIER-SANTOS, M. A. et al. The putrescine analogue 1,4-diamino-2-butanone affects polyamine synthesis, transport, ultrastructure and intracellular survival in Leishmania amazonensis. Microbiology, v. 154, n.10, p. 3104-3111. Oct. 2008.
1350-0872
10.1099/mic.0.2007/013896-0
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