NF-κB inhibitors impair platelet activation responses

Autores
Malaver Marín, Elisa; Romaniuk, María Albertina; D'Atri, Lina Paola; Pozner, Roberto Gabriel; Negrotto, Soledad; Benzadón, R.; Schattner, Mirta Ana
Año de publicación
2009
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Background: Although platelets are anucleated cells, they express several transcription factors that exert non-genomic functions, including the positive and negative regulation of platelet activation. NF-κB is a major transcriptional regulator of genes involved in survival, proliferation and inflammation. Objective: Because platelets play a critical role not only in hemostasis, but also in inflammation and tumor progression, we evaluated the role of NF-κB in platelet physiology. Results: Immunofluorescence, Western blotting and ELISA studies revealed that platelets express IκBα and NF-κB, and that stimulation with thrombin triggers IκBα phosphorylation and degradation and the binding of platelet NF-κB p65 subunit to synthetic olignoucleotides containing the consensus sequence for NF-κB. Two specific unrelated inhibitors of NF-κB activation, BAY 11-7082 and Ro 106-9920, reduced PAC-1 and fibrinogen binding to integrin αIIbβ3 and restricted platelet spreading on immobilized fibrinogen. Both inhibitors impaired aggregation mediated by ADP, epinephrine, collagen or thrombin, but not arachidonic acid. ATP release, TXB2 formation, P-selectin expression, ERK phosphorylation and cPLA2 activity stimulated by thrombin were reduced in BAY 11-7082- or Ro 106-9920-treated platelets. Although bleeding time was not affected, ADP-induced platelet aggregation was impaired in mice treated with BAY 11-7082. Conclusions: Our results suggest that NF-κB may be a novel mediator of platelet responses. The blockade of platelet function by NF-κB inhibitors might be relevant in those clinical situations where these drugs are being considered for anti-tumor and/or anti-inflammatory therapy. © 2009 International Society on Thrombosis and Haemostasis.
Fil: Malaver Marín, Elisa. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; Argentina
Fil: Romaniuk, María Albertina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; Argentina
Fil: D'Atri, Lina Paola. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; Argentina
Fil: Pozner, Roberto Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; Argentina
Fil: Negrotto, Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; Argentina
Fil: Benzadón, R.. Centro de Educación Medica E Invest.clinicas; Argentina
Fil: Schattner, Mirta Ana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; Argentina
Materia
ΑIibΒ3
Cpla2
Nf-ΚB
Platelets
Txb2
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/54503
Acceder
id CONICETDig_b1670406ac8dd0fa70b1a51131ae181f
oai_identifier_str oai:ri.conicet.gov.ar:11336/54503
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling NF-κB inhibitors impair platelet activation responsesMalaver Marín, ElisaRomaniuk, María AlbertinaD'Atri, Lina PaolaPozner, Roberto GabrielNegrotto, SoledadBenzadón, R.Schattner, Mirta AnaΑIibΒ3Cpla2Nf-ΚBPlateletsTxb2https://purl.org/becyt/ford/3.2https://purl.org/becyt/ford/3Background: Although platelets are anucleated cells, they express several transcription factors that exert non-genomic functions, including the positive and negative regulation of platelet activation. NF-κB is a major transcriptional regulator of genes involved in survival, proliferation and inflammation. Objective: Because platelets play a critical role not only in hemostasis, but also in inflammation and tumor progression, we evaluated the role of NF-κB in platelet physiology. Results: Immunofluorescence, Western blotting and ELISA studies revealed that platelets express IκBα and NF-κB, and that stimulation with thrombin triggers IκBα phosphorylation and degradation and the binding of platelet NF-κB p65 subunit to synthetic olignoucleotides containing the consensus sequence for NF-κB. Two specific unrelated inhibitors of NF-κB activation, BAY 11-7082 and Ro 106-9920, reduced PAC-1 and fibrinogen binding to integrin αIIbβ3 and restricted platelet spreading on immobilized fibrinogen. Both inhibitors impaired aggregation mediated by ADP, epinephrine, collagen or thrombin, but not arachidonic acid. ATP release, TXB2 formation, P-selectin expression, ERK phosphorylation and cPLA2 activity stimulated by thrombin were reduced in BAY 11-7082- or Ro 106-9920-treated platelets. Although bleeding time was not affected, ADP-induced platelet aggregation was impaired in mice treated with BAY 11-7082. Conclusions: Our results suggest that NF-κB may be a novel mediator of platelet responses. The blockade of platelet function by NF-κB inhibitors might be relevant in those clinical situations where these drugs are being considered for anti-tumor and/or anti-inflammatory therapy. © 2009 International Society on Thrombosis and Haemostasis.Fil: Malaver Marín, Elisa. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; ArgentinaFil: Romaniuk, María Albertina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; ArgentinaFil: D'Atri, Lina Paola. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; ArgentinaFil: Pozner, Roberto Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; ArgentinaFil: Negrotto, Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; ArgentinaFil: Benzadón, R.. Centro de Educación Medica E Invest.clinicas; ArgentinaFil: Schattner, Mirta Ana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; ArgentinaWiley Blackwell Publishing, Inc2009-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/54503Malaver Marín, Elisa; Romaniuk, María Albertina; D'Atri, Lina Paola; Pozner, Roberto Gabriel; Negrotto, Soledad; et al.; NF-κB inhibitors impair platelet activation responses; Wiley Blackwell Publishing, Inc; Journal of Thrombosis and Haemostasis; 7; 8; 12-2009; 1333-13431538-7933CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1111/j.1538-7836.2009.03492.xinfo:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1538-7836.2009.03492.xinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:43:21Zoai:ri.conicet.gov.ar:11336/54503instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 10:43:21.805CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv NF-κB inhibitors impair platelet activation responses
title NF-κB inhibitors impair platelet activation responses
spellingShingle NF-κB inhibitors impair platelet activation responses
Malaver Marín, Elisa
ΑIibΒ3
Cpla2
Nf-ΚB
Platelets
Txb2
title_short NF-κB inhibitors impair platelet activation responses
title_full NF-κB inhibitors impair platelet activation responses
title_fullStr NF-κB inhibitors impair platelet activation responses
title_full_unstemmed NF-κB inhibitors impair platelet activation responses
title_sort NF-κB inhibitors impair platelet activation responses
dc.creator.none.fl_str_mv Malaver Marín, Elisa
Romaniuk, María Albertina
D'Atri, Lina Paola
Pozner, Roberto Gabriel
Negrotto, Soledad
Benzadón, R.
Schattner, Mirta Ana
author Malaver Marín, Elisa
author_facet Malaver Marín, Elisa
Romaniuk, María Albertina
D'Atri, Lina Paola
Pozner, Roberto Gabriel
Negrotto, Soledad
Benzadón, R.
Schattner, Mirta Ana
author_role author
author2 Romaniuk, María Albertina
D'Atri, Lina Paola
Pozner, Roberto Gabriel
Negrotto, Soledad
Benzadón, R.
Schattner, Mirta Ana
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv ΑIibΒ3
Cpla2
Nf-ΚB
Platelets
Txb2
topic ΑIibΒ3
Cpla2
Nf-ΚB
Platelets
Txb2
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.2
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Background: Although platelets are anucleated cells, they express several transcription factors that exert non-genomic functions, including the positive and negative regulation of platelet activation. NF-κB is a major transcriptional regulator of genes involved in survival, proliferation and inflammation. Objective: Because platelets play a critical role not only in hemostasis, but also in inflammation and tumor progression, we evaluated the role of NF-κB in platelet physiology. Results: Immunofluorescence, Western blotting and ELISA studies revealed that platelets express IκBα and NF-κB, and that stimulation with thrombin triggers IκBα phosphorylation and degradation and the binding of platelet NF-κB p65 subunit to synthetic olignoucleotides containing the consensus sequence for NF-κB. Two specific unrelated inhibitors of NF-κB activation, BAY 11-7082 and Ro 106-9920, reduced PAC-1 and fibrinogen binding to integrin αIIbβ3 and restricted platelet spreading on immobilized fibrinogen. Both inhibitors impaired aggregation mediated by ADP, epinephrine, collagen or thrombin, but not arachidonic acid. ATP release, TXB2 formation, P-selectin expression, ERK phosphorylation and cPLA2 activity stimulated by thrombin were reduced in BAY 11-7082- or Ro 106-9920-treated platelets. Although bleeding time was not affected, ADP-induced platelet aggregation was impaired in mice treated with BAY 11-7082. Conclusions: Our results suggest that NF-κB may be a novel mediator of platelet responses. The blockade of platelet function by NF-κB inhibitors might be relevant in those clinical situations where these drugs are being considered for anti-tumor and/or anti-inflammatory therapy. © 2009 International Society on Thrombosis and Haemostasis.
Fil: Malaver Marín, Elisa. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; Argentina
Fil: Romaniuk, María Albertina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; Argentina
Fil: D'Atri, Lina Paola. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; Argentina
Fil: Pozner, Roberto Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; Argentina
Fil: Negrotto, Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; Argentina
Fil: Benzadón, R.. Centro de Educación Medica E Invest.clinicas; Argentina
Fil: Schattner, Mirta Ana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; Argentina
description Background: Although platelets are anucleated cells, they express several transcription factors that exert non-genomic functions, including the positive and negative regulation of platelet activation. NF-κB is a major transcriptional regulator of genes involved in survival, proliferation and inflammation. Objective: Because platelets play a critical role not only in hemostasis, but also in inflammation and tumor progression, we evaluated the role of NF-κB in platelet physiology. Results: Immunofluorescence, Western blotting and ELISA studies revealed that platelets express IκBα and NF-κB, and that stimulation with thrombin triggers IκBα phosphorylation and degradation and the binding of platelet NF-κB p65 subunit to synthetic olignoucleotides containing the consensus sequence for NF-κB. Two specific unrelated inhibitors of NF-κB activation, BAY 11-7082 and Ro 106-9920, reduced PAC-1 and fibrinogen binding to integrin αIIbβ3 and restricted platelet spreading on immobilized fibrinogen. Both inhibitors impaired aggregation mediated by ADP, epinephrine, collagen or thrombin, but not arachidonic acid. ATP release, TXB2 formation, P-selectin expression, ERK phosphorylation and cPLA2 activity stimulated by thrombin were reduced in BAY 11-7082- or Ro 106-9920-treated platelets. Although bleeding time was not affected, ADP-induced platelet aggregation was impaired in mice treated with BAY 11-7082. Conclusions: Our results suggest that NF-κB may be a novel mediator of platelet responses. The blockade of platelet function by NF-κB inhibitors might be relevant in those clinical situations where these drugs are being considered for anti-tumor and/or anti-inflammatory therapy. © 2009 International Society on Thrombosis and Haemostasis.
publishDate 2009
dc.date.none.fl_str_mv 2009-12
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/54503
Malaver Marín, Elisa; Romaniuk, María Albertina; D'Atri, Lina Paola; Pozner, Roberto Gabriel; Negrotto, Soledad; et al.; NF-κB inhibitors impair platelet activation responses; Wiley Blackwell Publishing, Inc; Journal of Thrombosis and Haemostasis; 7; 8; 12-2009; 1333-1343
1538-7933
CONICET Digital
CONICET
url http://hdl.handle.net/11336/54503
identifier_str_mv Malaver Marín, Elisa; Romaniuk, María Albertina; D'Atri, Lina Paola; Pozner, Roberto Gabriel; Negrotto, Soledad; et al.; NF-κB inhibitors impair platelet activation responses; Wiley Blackwell Publishing, Inc; Journal of Thrombosis and Haemostasis; 7; 8; 12-2009; 1333-1343
1538-7933
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1111/j.1538-7836.2009.03492.x
info:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1538-7836.2009.03492.x
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Wiley Blackwell Publishing, Inc
publisher.none.fl_str_mv Wiley Blackwell Publishing, Inc
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.070432

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