Dengue induces platelet activation, mitochondrial dysfunction and cell death through mechanisms that involve DC-SIGN and caspases

Detalhes bibliográficos
Autor(a) principal: Hottz, E. D.
Data de Publicação: 2013
Outros Autores: 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.
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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spelling 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:icict/11774TElDRU7Dh0EgREUgRElTVFJJQlVJw4fDg08gTsODTy1FWENMVVNJVkEKCkFvIGNvbmNvcmRhciBlIGFjZWl0YXIgZXN0YSBsaWNlbsOnYSB2b2PDqiAoYXV0b3Igb3UgZGV0ZW50b3IgZG9zIGRpcmVpdG9zIGF1dG9yYWlzKToKCmEpIERlY2xhcmEgcXVlIGNvbmhlY2UgYSBwb2zDrXRpY2EgZGUgY29weXJpZ2h0IGRhIGVkaXRvcmEgZG8gc2V1IGRvY3VtZW50by4KCmIpIERlY2xhcmEgcXVlIGNvbmhlY2UgZSBhY2VpdGEgYXMgRGlyZXRyaXplcyBwYXJhIG8gUmVwb3NpdMOzcmlvIEluc3RpdHVjaW9uYWwgZGEgRnVuZGHDp8OjbyBPc3dhbGRvIENydXogKEZJT0NSVVopLgoKYykgQ29uY2VkZSDDoCBGSU9DUlVaIG8gZGlyZWl0byBuw6NvLWV4Y2x1c2l2byBkZSBhcnF1aXZhciwgcmVwcm9kdXppciwgY29udmVydGVyIChjb21vIGRlZmluaWRvIGEgc2VndWlyKSwgY29tdW5pY2FyCiAKZS9vdSBkaXN0cmlidWlyIG5vIFJlcG9zaXTDs3JpbyBkYSBGSU9DUlVaLCBvIGRvY3VtZW50byBlbnRyZWd1ZSAoaW5jbHVpbmRvIG8gcmVzdW1vL2Fic3RyYWN0KSBlbSBmb3JtYXRvIGRpZ2l0YWwgb3UgCgpwb3IgcXVhbHF1ZXIgb3V0cm8gbWVpby4KCmQpIERlY2xhcmEgcXVlIGF1dG9yaXphIGEgRklPQ1JVWiBhIGFycXVpdmFyIG1haXMgZGUgdW1hIGPDs3BpYSBkZXN0ZSBkb2N1bWVudG8gZSBjb252ZXJ0w6otbG8sIHNlbSBhbHRlcmFyIG8gc2V1IGNvbnRlw7pkbywgCgpwYXJhIHF1YWxxdWVyIGZvcm1hdG8gZGUgYXJxdWl2bywgbWVpbyBvdSBzdXBvcnRlLCBwYXJhIGVmZWl0b3MgZGUgc2VndXJhbsOnYSwgcHJlc2VydmHDp8OjbyAoYmFja3VwKSBlIGFjZXNzby4KCmUpIERlY2xhcmEgcXVlIG8gZG9jdW1lbnRvIHN1Ym1ldGlkbyDDqSBvIHNldSB0cmFiYWxobyBvcmlnaW5hbCwgZSBxdWUgZGV0w6ltIG8gZGlyZWl0byBkZSBjb25jZWRlciBhIHRlcmNlaXJvcyBvcyBkaXJlaXRvcyAKCmNvbnRpZG9zIG5lc3RhIGxpY2Vuw6dhLiBEZWNsYXJhIHRhbWLDqW0gcXVlIGEgZW50cmVnYSBkbyBkb2N1bWVudG8gbsOjbyBpbmZyaW5nZSBvcyBkaXJlaXRvcyBkZSBxdWFscXVlciBvdXRyYSBwZXNzb2Egb3UgZW50aWRhZGUuCgpmKSBEZWNsYXJhIHF1ZSwgbm8gY2FzbyBkbyBkb2N1bWVudG8gc3VibWV0aWRvIGNvbnRlciBtYXRlcmlhbCBkbyBxdWFsIG7Do28gZGV0w6ltIG9zIGRpcmVpdG9zIGRlIGF1dG9yLCBvYnRldmUgYSBhdXRvcml6YcOnw6NvIAoKaXJyZXN0cml0YSBkbyByZXNwZWN0aXZvIGRldGVudG9yIGRlc3NlcyBkaXJlaXRvcywgcGFyYSBjZWRlciBhIEZJT0NSVVogb3MgZGlyZWl0b3MgcmVxdWVyaWRvcyBwb3IgZXN0YSBMaWNlbsOnYSBlIGF1dG9yaXphciBhIAoKdXRpbGl6w6EtbG9zIGxlZ2FsbWVudGUuIERlY2xhcmEgdGFtYsOpbSBxdWUgZXNzZSBtYXRlcmlhbCBjdWpvcyBkaXJlaXRvcyBzw6NvIGRlIHRlcmNlaXJvcyBlc3TDoSBjbGFyYW1lbnRlIGlkZW50aWZpY2FkbyBlIHJlY29uaGVjaWRvIAoKbm8gdGV4dG8gb3UgY29udGXDumRvIGRvIGRvY3VtZW50byBlbnRyZWd1ZS4KCmcpIFNFIE8gRE9DVU1FTlRPIEVOVFJFR1VFIMOJIEJBU0VBRE8gRU0gVFJBQkFMSE8gRklOQU5DSUFETyBPVSBBUE9JQURPIFBPUiBPVVRSQSBJTlNUSVRVScOHw4NPIFFVRSBOw4NPIEEgRklPQ1JVWiwgREVDTEFSQSBRVUUgQ1VNUFJJVSAKClFVQUlTUVVFUiBPQlJJR0HDh8OVRVMgRVhJR0lEQVMgUEVMTyBSRVNQRUNUSVZPIENPTlRSQVRPIE9VIEFDT1JETy4gQSBGSU9DUlVaIGlkZW50aWZpY2Fyw6EgY2xhcmFtZW50ZSBvKHMpIG5vbWUocykgZG8ocykgYXV0b3IoZXMpIGRvcyAKCmRpcmVpdG9zIGRvIGRvY3VtZW50byBlbnRyZWd1ZSBlIG7Do28gZmFyw6EgcXVhbHF1ZXIgYWx0ZXJhw6fDo28sIHBhcmEgYWzDqW0gZG8gcHJldmlzdG8gbmEgYWzDrW5lYSBjKS4KRepositório 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
url https://www.arca.fiocruz.br/handle/icict/11774
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Wiley Online Library
publisher.none.fl_str_mv Wiley Online Library
dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
instname:Fundação Oswaldo Cruz (FIOCRUZ)
instacron:FIOCRUZ
instname_str Fundação Oswaldo Cruz (FIOCRUZ)
instacron_str FIOCRUZ
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reponame_str Repositório Institucional da FIOCRUZ (ARCA)
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