Dengue induces platelet activation, mitochondrial dysfunction and cell death through mechanisms that involve DC-SIGN and caspases
Autor(a) principal: | |
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Data de Publicação: | 2013 |
Outros Autores: | , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da FIOCRUZ (ARCA) |
Texto Completo: | https://www.arca.fiocruz.br/handle/icict/11774 |
Resumo: | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Instituto de Pesquisa Clinica Evandro Chagas. Rio de Janeiro, RJ, Brasil / |
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Hottz, E. D.Oliveira, M. F.Nunes, P. C. G.Nogueira, R. M. R.Souza, R. Valls dePoian, A. T. daWeyrich, A. S.Zimmerman, G. A.Bozza, P. T.Bozza, F. A.2015-09-21T17:25:45Z2015-09-21T17:25:45Z2013HOTTZ, E. D.; et al. Dengue induces platelet activation, mitochondrial dysfunction and cell death through mechanisms that involve DC-SIGN and caspases. Journal of Thrombosis and Haemostasis, v.11, n.5, p.951–962, May 2013.1538-7836https://www.arca.fiocruz.br/handle/icict/1177410.1111/jth.12178engWiley Online LibraryDengue induces platelet activation, mitochondrial dysfunction and cell death through mechanisms that involve DC-SIGN and caspasesinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Instituto de Pesquisa Clinica Evandro Chagas. Rio de Janeiro, RJ, Brasil /Universidade Federal do Rio de Janeiro. Instituto de Bioquíımica Médica. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Flavivírus. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Flavivírus. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto de Pesquisa Clínica Evandro Chagas. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Bioquíımica Médica. Rio de Janeiro, RJ, Brasil.University of Utah. The Molecular Medicine Program. Department of Medicine. Salt Lake City, UT, USA.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto de Pesquisa Clínica Evandro Chagas. Rio de Janeiro, RJ, Brasil.Background: Worldwide, dengue is the most prevalent human arbovirus disease. Dengue infection may cause a range of clinical manifestations from self-limiting febrile illness through to a life-threatening syndrome accompanied by both bleeding and shock. Thrombocytopenia is frequently observed in mild and severe disease; however, the mechanisms involved in DENV-induced platelet activation and thrombocytopenia are incompletely understood. Patients and methods: Freshly isolated platelets from patients with dengue were evaluated for markers of activation, mitochondrial alteration and activation of cell death pathways. In parallel, we examined direct DENV-induced activation and apoptosis of platelets obtained from healthy subjects. Results: We found that platelets from DENVinfected patients exhibited increased activation by comparison to control subjects. Moreover, platelets from DENVinfected patients exhibited classic signs of the intrinsic pathway of apoptosis that include increased surface phosphatidylserine exposure, mitochondrial depolarization and activation of caspase-9 and -3. Indeed, thrombocytopenia was shown to strongly associate with enhanced platelet activation and cell death in DENV-infected patients. Platelet activation, mitochondrial dysfunction and caspasedependent phosphatidylserine exposure on platelets were also observed when platelets from healthy subjects were directly exposed to DENV in vitro. DENV-induced platelet activation was shown to occur through mechanisms largely dependent on DC-SIGN. Conclusions: : Together our results demonstrate that platelets from patients with dengue present signs of activation, mitochondrial dysfunction and activation of the apoptosis caspase cascade, which may contribute to the development of thrombocytopenia in patients with dengue. Our results also suggest the involvement of DC-SIGN as a critical receptor in DENV-dependent platelet activation.ApoptosisDC-SIGNDengueMitochondrial dysfunctionPlatelet activationThrombocytopeniDengueTrombocitopeniaApoptoseAtivação Plaquetáriainfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txttext/plain1914https://www.arca.fiocruz.br/bitstream/icict/11774/1/license.txt7d48279ffeed55da8dfe2f8e81f3b81fMD51ORIGINALed_hottz_etal_IOC_2013.pdfapplication/pdf542019https://www.arca.fiocruz.br/bitstream/icict/11774/2/ed_hottz_etal_IOC_2013.pdfbd45f9afa5faa617313440398fd6efc1MD52TEXTed_hottz_etal_IOC_2013.pdf.txted_hottz_etal_IOC_2013.pdf.txtExtracted texttext/plain47810https://www.arca.fiocruz.br/bitstream/icict/11774/3/ed_hottz_etal_IOC_2013.pdf.txt7a9b60a070c99bffe2d85d8729f39267MD53icict/117742022-06-24 12:18:58.435oai:www.arca.fiocruz.br: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ório InstitucionalPUBhttps://www.arca.fiocruz.br/oai/requestrepositorio.arca@fiocruz.bropendoar:21352022-06-24T15:18:58Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)false |
dc.title.pt_BR.fl_str_mv |
Dengue induces platelet activation, mitochondrial dysfunction and cell death through mechanisms that involve DC-SIGN and caspases |
title |
Dengue induces platelet activation, mitochondrial dysfunction and cell death through mechanisms that involve DC-SIGN and caspases |
spellingShingle |
Dengue induces platelet activation, mitochondrial dysfunction and cell death through mechanisms that involve DC-SIGN and caspases Hottz, E. D. Apoptosis DC-SIGN Dengue Mitochondrial dysfunction Platelet activation Thrombocytopeni Dengue Trombocitopenia Apoptose Ativação Plaquetária |
title_short |
Dengue induces platelet activation, mitochondrial dysfunction and cell death through mechanisms that involve DC-SIGN and caspases |
title_full |
Dengue induces platelet activation, mitochondrial dysfunction and cell death through mechanisms that involve DC-SIGN and caspases |
title_fullStr |
Dengue induces platelet activation, mitochondrial dysfunction and cell death through mechanisms that involve DC-SIGN and caspases |
title_full_unstemmed |
Dengue induces platelet activation, mitochondrial dysfunction and cell death through mechanisms that involve DC-SIGN and caspases |
title_sort |
Dengue induces platelet activation, mitochondrial dysfunction and cell death through mechanisms that involve DC-SIGN and caspases |
author |
Hottz, E. D. |
author_facet |
Hottz, E. D. Oliveira, M. F. Nunes, P. C. G. Nogueira, R. M. R. Souza, R. Valls de Poian, A. T. da Weyrich, A. S. Zimmerman, G. A. Bozza, P. T. Bozza, F. A. |
author_role |
author |
author2 |
Oliveira, M. F. Nunes, P. C. G. Nogueira, R. M. R. Souza, R. Valls de Poian, A. T. da Weyrich, A. S. Zimmerman, G. A. Bozza, P. T. Bozza, F. A. |
author2_role |
author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Hottz, E. D. Oliveira, M. F. Nunes, P. C. G. Nogueira, R. M. R. Souza, R. Valls de Poian, A. T. da Weyrich, A. S. Zimmerman, G. A. Bozza, P. T. Bozza, F. A. |
dc.subject.en.pt_BR.fl_str_mv |
Apoptosis DC-SIGN Dengue Mitochondrial dysfunction Platelet activation Thrombocytopeni |
topic |
Apoptosis DC-SIGN Dengue Mitochondrial dysfunction Platelet activation Thrombocytopeni Dengue Trombocitopenia Apoptose Ativação Plaquetária |
dc.subject.decs.pt_BR.fl_str_mv |
Dengue Trombocitopenia Apoptose Ativação Plaquetária |
description |
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Instituto de Pesquisa Clinica Evandro Chagas. Rio de Janeiro, RJ, Brasil / |
publishDate |
2013 |
dc.date.issued.fl_str_mv |
2013 |
dc.date.accessioned.fl_str_mv |
2015-09-21T17:25:45Z |
dc.date.available.fl_str_mv |
2015-09-21T17:25:45Z |
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 |
HOTTZ, E. D.; et al. Dengue induces platelet activation, mitochondrial dysfunction and cell death through mechanisms that involve DC-SIGN and caspases. Journal of Thrombosis and Haemostasis, v.11, n.5, p.951–962, May 2013. |
dc.identifier.uri.fl_str_mv |
https://www.arca.fiocruz.br/handle/icict/11774 |
dc.identifier.issn.pt_BR.fl_str_mv |
1538-7836 |
dc.identifier.doi.pt_BR.fl_str_mv |
10.1111/jth.12178 |
identifier_str_mv |
HOTTZ, E. D.; et al. Dengue induces platelet activation, mitochondrial dysfunction and cell death through mechanisms that involve DC-SIGN and caspases. Journal of Thrombosis and Haemostasis, v.11, n.5, p.951–962, May 2013. 1538-7836 10.1111/jth.12178 |
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https://www.arca.fiocruz.br/handle/icict/11774 |
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eng |
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eng |
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info:eu-repo/semantics/openAccess |
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openAccess |
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Wiley Online Library |
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Wiley Online Library |
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reponame:Repositório Institucional da FIOCRUZ (ARCA) instname:Fundação Oswaldo Cruz (FIOCRUZ) instacron:FIOCRUZ |
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Fundação Oswaldo Cruz (FIOCRUZ) |
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