Characterization of dual effects induced by antimicrobial peptides: Regulated cell death or membrane disruption
Autor(a) principal: | |
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Data de Publicação: | 2012 |
Outros Autores: | , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNIFESP |
Texto Completo: | http://repositorio.unifesp.br/handle/11600/35009 http://dx.doi.org/10.1016/j.bbagen.2012.02.015 |
Resumo: | Background: Some reports describe lysis mechanisms by antimicrobial peptides (AMPs), while others describe the activation of regulated cell death. in this study, we compare the cell death-inducing activities of four beta-hairpin AMPs (gomesin, protegrin, tachyplesin and polyphemusin II) along with their linear analogs in the human erythroleukemia K562 cell line to investigate the relationship between their structure and activity.Methods: K562 cells were exposed to AMPs. Morphological and biochemistry alterations were evaluated using light microscopy, confocal microscopy and flow cytometry.Results: Gomesin and protegrin displayed cytotoxic properties that their linear counterparts did not. Tachyplesin and polyphemusin II and also their linear analogs induced cell death. We were able to distinguish two ways in which these AMPs induced cell death. Lower concentrations of AMPs induced controlled cell death mechanisms. Gomesin, tachyplesin and linear-tachyplesin promoted apoptosis that was characterized by annexin labeling, sensitivity to Z-VAD, and caspase-3 activation, but was also inhibited by necrostatin-1. Gomesin and protegrin induced cell death was dependent on intracellular Ca2+ mechanisms and the participation of free radicals was observed in protegrin induced cell death. Polyphemusin II and its linear analog mainly induced necrosis. Conversely, treatment with higher concentrations of AMPs primarily resulted in cell membrane disruption, but with clearly different patterns of action for each AMP tested.Conclusion: Different actions by beta-hairpin AMPs were observed at low concentrations and at higher concentrations despite the structure similarity.General significance: Controlled intracellular mechanism and direct membrane disruption were clearly distinguished helping to understand the real action of AMPs in mammalian cells. (C) 2012 Elsevier B.V. All rights reserved. |
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Paredes-Gamero, Edgar Julian [UNIFESP]Martins, Marta Natividade Crizol [UNIFESP]Cappabianco, Fabio Augusto Menocci [UNIFESP]Ide, Jaime Shinsuke [UNIFESP]Miranda, Antonio [UNIFESP]Universidade Federal de São Paulo (UNIFESP)2016-01-24T14:27:23Z2016-01-24T14:27:23Z2012-07-01Biochimica Et Biophysica Acta-general Subjects. Amsterdam: Elsevier B.V., v. 1820, n. 7, p. 1062-1072, 2012.0304-4165http://repositorio.unifesp.br/handle/11600/35009http://dx.doi.org/10.1016/j.bbagen.2012.02.015WOS000305366100033.pdf10.1016/j.bbagen.2012.02.015WOS:000305366100033Background: Some reports describe lysis mechanisms by antimicrobial peptides (AMPs), while others describe the activation of regulated cell death. in this study, we compare the cell death-inducing activities of four beta-hairpin AMPs (gomesin, protegrin, tachyplesin and polyphemusin II) along with their linear analogs in the human erythroleukemia K562 cell line to investigate the relationship between their structure and activity.Methods: K562 cells were exposed to AMPs. Morphological and biochemistry alterations were evaluated using light microscopy, confocal microscopy and flow cytometry.Results: Gomesin and protegrin displayed cytotoxic properties that their linear counterparts did not. Tachyplesin and polyphemusin II and also their linear analogs induced cell death. We were able to distinguish two ways in which these AMPs induced cell death. Lower concentrations of AMPs induced controlled cell death mechanisms. Gomesin, tachyplesin and linear-tachyplesin promoted apoptosis that was characterized by annexin labeling, sensitivity to Z-VAD, and caspase-3 activation, but was also inhibited by necrostatin-1. Gomesin and protegrin induced cell death was dependent on intracellular Ca2+ mechanisms and the participation of free radicals was observed in protegrin induced cell death. Polyphemusin II and its linear analog mainly induced necrosis. Conversely, treatment with higher concentrations of AMPs primarily resulted in cell membrane disruption, but with clearly different patterns of action for each AMP tested.Conclusion: Different actions by beta-hairpin AMPs were observed at low concentrations and at higher concentrations despite the structure similarity.General significance: Controlled intracellular mechanism and direct membrane disruption were clearly distinguished helping to understand the real action of AMPs in mammalian cells. (C) 2012 Elsevier B.V. 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)Universidade Federal de São Paulo, Dept Bioquim, BR-04044020 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Biofis, BR-04044020 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Ciencia & Tecnol, BR-12231280 Sao Jose Dos Campos, SP, BrazilUniversidade Federal de São Paulo, Dept Bioquim, BR-04044020 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Biofis, BR-04044020 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Ciencia & Tecnol, BR-12231280 Sao Jose Dos Campos, SP, BrazilFAPESP: 2009/54869-2FAPESP: 2011/17584-0Web of Science1062-1072engElsevier B.V.Biochimica Et Biophysica Acta-general Subjectshttp://www.elsevier.com/about/open-access/open-access-policies/article-posting-policyinfo:eu-repo/semantics/openAccessAntimicrobial peptideCell deathMembrane permeabilizationIntracellular mechanismCharacterization of dual effects induced by antimicrobial peptides: Regulated cell death or membrane disruptioninfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlereponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESPORIGINALWOS000305366100033.pdfapplication/pdf1915206${dspace.ui.url}/bitstream/11600/35009/1/WOS000305366100033.pdfd000739ad3cddd789d51e4459706fbc5MD51open accessTEXTWOS000305366100033.pdf.txtWOS000305366100033.pdf.txtExtracted texttext/plain52960${dspace.ui.url}/bitstream/11600/35009/9/WOS000305366100033.pdf.txt76940b9774b1e62afa866c5a4f44d6f3MD59open accessTHUMBNAILWOS000305366100033.pdf.jpgWOS000305366100033.pdf.jpgIM Thumbnailimage/jpeg7623${dspace.ui.url}/bitstream/11600/35009/11/WOS000305366100033.pdf.jpgab15f1859bb609dfffabc46e3a0b5b5fMD511open access11600/350092023-06-05 19:06:56.639open accessoai:repositorio.unifesp.br:11600/35009Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestopendoar:34652023-06-05T22:06:56Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false |
dc.title.en.fl_str_mv |
Characterization of dual effects induced by antimicrobial peptides: Regulated cell death or membrane disruption |
title |
Characterization of dual effects induced by antimicrobial peptides: Regulated cell death or membrane disruption |
spellingShingle |
Characterization of dual effects induced by antimicrobial peptides: Regulated cell death or membrane disruption Paredes-Gamero, Edgar Julian [UNIFESP] Antimicrobial peptide Cell death Membrane permeabilization Intracellular mechanism |
title_short |
Characterization of dual effects induced by antimicrobial peptides: Regulated cell death or membrane disruption |
title_full |
Characterization of dual effects induced by antimicrobial peptides: Regulated cell death or membrane disruption |
title_fullStr |
Characterization of dual effects induced by antimicrobial peptides: Regulated cell death or membrane disruption |
title_full_unstemmed |
Characterization of dual effects induced by antimicrobial peptides: Regulated cell death or membrane disruption |
title_sort |
Characterization of dual effects induced by antimicrobial peptides: Regulated cell death or membrane disruption |
author |
Paredes-Gamero, Edgar Julian [UNIFESP] |
author_facet |
Paredes-Gamero, Edgar Julian [UNIFESP] Martins, Marta Natividade Crizol [UNIFESP] Cappabianco, Fabio Augusto Menocci [UNIFESP] Ide, Jaime Shinsuke [UNIFESP] Miranda, Antonio [UNIFESP] |
author_role |
author |
author2 |
Martins, Marta Natividade Crizol [UNIFESP] Cappabianco, Fabio Augusto Menocci [UNIFESP] Ide, Jaime Shinsuke [UNIFESP] Miranda, Antonio [UNIFESP] |
author2_role |
author author author author |
dc.contributor.institution.none.fl_str_mv |
Universidade Federal de São Paulo (UNIFESP) |
dc.contributor.author.fl_str_mv |
Paredes-Gamero, Edgar Julian [UNIFESP] Martins, Marta Natividade Crizol [UNIFESP] Cappabianco, Fabio Augusto Menocci [UNIFESP] Ide, Jaime Shinsuke [UNIFESP] Miranda, Antonio [UNIFESP] |
dc.subject.eng.fl_str_mv |
Antimicrobial peptide Cell death Membrane permeabilization Intracellular mechanism |
topic |
Antimicrobial peptide Cell death Membrane permeabilization Intracellular mechanism |
description |
Background: Some reports describe lysis mechanisms by antimicrobial peptides (AMPs), while others describe the activation of regulated cell death. in this study, we compare the cell death-inducing activities of four beta-hairpin AMPs (gomesin, protegrin, tachyplesin and polyphemusin II) along with their linear analogs in the human erythroleukemia K562 cell line to investigate the relationship between their structure and activity.Methods: K562 cells were exposed to AMPs. Morphological and biochemistry alterations were evaluated using light microscopy, confocal microscopy and flow cytometry.Results: Gomesin and protegrin displayed cytotoxic properties that their linear counterparts did not. Tachyplesin and polyphemusin II and also their linear analogs induced cell death. We were able to distinguish two ways in which these AMPs induced cell death. Lower concentrations of AMPs induced controlled cell death mechanisms. Gomesin, tachyplesin and linear-tachyplesin promoted apoptosis that was characterized by annexin labeling, sensitivity to Z-VAD, and caspase-3 activation, but was also inhibited by necrostatin-1. Gomesin and protegrin induced cell death was dependent on intracellular Ca2+ mechanisms and the participation of free radicals was observed in protegrin induced cell death. Polyphemusin II and its linear analog mainly induced necrosis. Conversely, treatment with higher concentrations of AMPs primarily resulted in cell membrane disruption, but with clearly different patterns of action for each AMP tested.Conclusion: Different actions by beta-hairpin AMPs were observed at low concentrations and at higher concentrations despite the structure similarity.General significance: Controlled intracellular mechanism and direct membrane disruption were clearly distinguished helping to understand the real action of AMPs in mammalian cells. (C) 2012 Elsevier B.V. All rights reserved. |
publishDate |
2012 |
dc.date.issued.fl_str_mv |
2012-07-01 |
dc.date.accessioned.fl_str_mv |
2016-01-24T14:27:23Z |
dc.date.available.fl_str_mv |
2016-01-24T14:27:23Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
Biochimica Et Biophysica Acta-general Subjects. Amsterdam: Elsevier B.V., v. 1820, n. 7, p. 1062-1072, 2012. |
dc.identifier.uri.fl_str_mv |
http://repositorio.unifesp.br/handle/11600/35009 http://dx.doi.org/10.1016/j.bbagen.2012.02.015 |
dc.identifier.issn.none.fl_str_mv |
0304-4165 |
dc.identifier.file.none.fl_str_mv |
WOS000305366100033.pdf |
dc.identifier.doi.none.fl_str_mv |
10.1016/j.bbagen.2012.02.015 |
dc.identifier.wos.none.fl_str_mv |
WOS:000305366100033 |
identifier_str_mv |
Biochimica Et Biophysica Acta-general Subjects. Amsterdam: Elsevier B.V., v. 1820, n. 7, p. 1062-1072, 2012. 0304-4165 WOS000305366100033.pdf 10.1016/j.bbagen.2012.02.015 WOS:000305366100033 |
url |
http://repositorio.unifesp.br/handle/11600/35009 http://dx.doi.org/10.1016/j.bbagen.2012.02.015 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.ispartof.none.fl_str_mv |
Biochimica Et Biophysica Acta-general Subjects |
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http://www.elsevier.com/about/open-access/open-access-policies/article-posting-policy info:eu-repo/semantics/openAccess |
rights_invalid_str_mv |
http://www.elsevier.com/about/open-access/open-access-policies/article-posting-policy |
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openAccess |
dc.format.none.fl_str_mv |
1062-1072 |
dc.publisher.none.fl_str_mv |
Elsevier B.V. |
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Elsevier B.V. |
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reponame:Repositório Institucional da UNIFESP instname:Universidade Federal de São Paulo (UNIFESP) instacron:UNIFESP |
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Universidade Federal de São Paulo (UNIFESP) |
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