Plasma kallikrein enhances platelet aggregation response by subthreshold doses of ADP

Detalhes bibliográficos
Autor(a) principal: Ottaiano, Tatiana F.
Data de Publicação: 2017
Outros Autores: Andrade, Sheila S., Oliveira, Cleide de, Silva, Mariana C. C., Buri, Marcus V., Juliano, Maria A., Girao, Manoel J. B. C., Sampaio, Misako U., Schmaier, Alvin H., Wlodawer, Alexander, Maffei, Francisco H. A. [UNESP], Oliva, Maria Luiza V.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UNESP
Texto Completo: http://dx.doi.org/10.1016/j.biochi.2017.01.010
http://hdl.handle.net/11449/162628
Resumo: Human plasma kallikrein (huPK) potentiates platelet responses to subthreshold doses of ADP, although huPK itself, does not induce platelet aggregation. In the present investigation, we observe that huPK pretreatment of platelets potentiates ADP-induced platelet activation by prior proteolysis of the G-protein -coupled receptor PAR-1. The potentiation of ADP-induced platelet activation by huPK is mediated by the integrin alpha(IIb)beta(3) through interactions with the KGD/KGE sequence motif in huPK. Integrin alpha(IIb)beta(3) is a cofactor for huPK binding to platelets to support PAR-1 hydrolysis that contributes to activation of the ADP signaling pathway. This activation pathway leads to phosphorylation of Src, AktS(473), ERK1/2, and p38 MAPK, and to Cat(2+) release. The effect of huPK is blocked by specific antagonists of PAR-1 (SCH 19197) and alpha(IIb)beta(3) (abciximab) and by synthetic peptides comprising the KGD and KGE sequence motifs of huPK. Further, recombinant plasma kallikrein inhibitor, rBbKI, also blocks this entire mechanism. These results suggest a new function for huPK. Formation of plasma kallikrein lowers the threshold for ADP-induced platelet activation. The present observations are consistent with the notion that plasma kallikrein promotes vascular disease and thrombosis in the intravascular compartment and its inhibition may ameliorate cardiovascular disease and thrombosis. (C) 2017 Elsevier B.V. and Societe Francaise de Biochimie et Biologie Moleculaire (SFBBM). All rights reserved.
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spelling Plasma kallikrein enhances platelet aggregation response by subthreshold doses of ADPADPIntegrin alphallbbeta3Plasma kallikreinPlatelet aggregationHuman plasma kallikrein (huPK) potentiates platelet responses to subthreshold doses of ADP, although huPK itself, does not induce platelet aggregation. In the present investigation, we observe that huPK pretreatment of platelets potentiates ADP-induced platelet activation by prior proteolysis of the G-protein -coupled receptor PAR-1. The potentiation of ADP-induced platelet activation by huPK is mediated by the integrin alpha(IIb)beta(3) through interactions with the KGD/KGE sequence motif in huPK. Integrin alpha(IIb)beta(3) is a cofactor for huPK binding to platelets to support PAR-1 hydrolysis that contributes to activation of the ADP signaling pathway. This activation pathway leads to phosphorylation of Src, AktS(473), ERK1/2, and p38 MAPK, and to Cat(2+) release. The effect of huPK is blocked by specific antagonists of PAR-1 (SCH 19197) and alpha(IIb)beta(3) (abciximab) and by synthetic peptides comprising the KGD and KGE sequence motifs of huPK. Further, recombinant plasma kallikrein inhibitor, rBbKI, also blocks this entire mechanism. These results suggest a new function for huPK. Formation of plasma kallikrein lowers the threshold for ADP-induced platelet activation. The present observations are consistent with the notion that plasma kallikrein promotes vascular disease and thrombosis in the intravascular compartment and its inhibition may ameliorate cardiovascular disease and thrombosis. (C) 2017 Elsevier B.V. and Societe Francaise de Biochimie et Biologie Moleculaire (SFBBM). All rights reserved.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Associacao Beneficente de Coleta de Sangue do Estado de Sao Paulo (COLSAN)NIHNational Cancer Institute, Center for Cancer ResearchUniv Fed Sao Paulo, Dept Biochem, Rua Tres Maio 100, BR-04044020 Sao Paulo, BrazilUniv Fed Sao Paulo, Dept Gynecol, BR-04024002 Sao Paulo, BrazilUniv Fed Sao Paulo, Dept Biophys, BR-04044020 Sao Paulo, BrazilCharitable Assoc Blood Collect COLSAN, Sao Paulo, SP, BrazilCase Western Reserve Univ, Cleveland, OH 44106 USAUniv Hosp Cleveland, Med Ctr, Cleveland, OH 44106 USANCI, Macromol Crystallog Lab, Ctr Canc Res, Frederick, MD 21701 USAUniv Estadual Paulista, Dept Orthoped & Surg, Botucatu, SP, BrazilUniv Estadual Paulista, Dept Orthoped & Surg, Botucatu, SP, BrazilFAPESP: 2009/53766-5FAPESP: 2012/19780-3CAPES: AUXPE 140/2015CAPES: 23038.007776/2014-32CNPq: 142009/2012-1Elsevier B.V.Universidade Federal de São Paulo (UNIFESP)Charitable Assoc Blood Collect COLSANCase Western Reserve UnivUniv Hosp ClevelandNCIUniversidade Estadual Paulista (Unesp)Ottaiano, Tatiana F.Andrade, Sheila S.Oliveira, Cleide deSilva, Mariana C. C.Buri, Marcus V.Juliano, Maria A.Girao, Manoel J. B. C.Sampaio, Misako U.Schmaier, Alvin H.Wlodawer, AlexanderMaffei, Francisco H. A. [UNESP]Oliva, Maria Luiza V.2018-11-26T17:21:13Z2018-11-26T17:21:13Z2017-04-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article72-81application/pdfhttp://dx.doi.org/10.1016/j.biochi.2017.01.010Biochimie. Paris: Elsevier France-editions Scientifiques Medicales Elsevier, v. 135, p. 72-81, 2017.0300-9084http://hdl.handle.net/11449/16262810.1016/j.biochi.2017.01.010WOS:000397694600009WOS000397694600009.pdfWeb of Sciencereponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengBiochimie1,554info:eu-repo/semantics/openAccess2024-08-14T14:19:05Zoai:repositorio.unesp.br:11449/162628Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-14T14:19:05Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false
dc.title.none.fl_str_mv Plasma kallikrein enhances platelet aggregation response by subthreshold doses of ADP
title Plasma kallikrein enhances platelet aggregation response by subthreshold doses of ADP
spellingShingle Plasma kallikrein enhances platelet aggregation response by subthreshold doses of ADP
Ottaiano, Tatiana F.
ADP
Integrin alphallbbeta3
Plasma kallikrein
Platelet aggregation
title_short Plasma kallikrein enhances platelet aggregation response by subthreshold doses of ADP
title_full Plasma kallikrein enhances platelet aggregation response by subthreshold doses of ADP
title_fullStr Plasma kallikrein enhances platelet aggregation response by subthreshold doses of ADP
title_full_unstemmed Plasma kallikrein enhances platelet aggregation response by subthreshold doses of ADP
title_sort Plasma kallikrein enhances platelet aggregation response by subthreshold doses of ADP
author Ottaiano, Tatiana F.
author_facet Ottaiano, Tatiana F.
Andrade, Sheila S.
Oliveira, Cleide de
Silva, Mariana C. C.
Buri, Marcus V.
Juliano, Maria A.
Girao, Manoel J. B. C.
Sampaio, Misako U.
Schmaier, Alvin H.
Wlodawer, Alexander
Maffei, Francisco H. A. [UNESP]
Oliva, Maria Luiza V.
author_role author
author2 Andrade, Sheila S.
Oliveira, Cleide de
Silva, Mariana C. C.
Buri, Marcus V.
Juliano, Maria A.
Girao, Manoel J. B. C.
Sampaio, Misako U.
Schmaier, Alvin H.
Wlodawer, Alexander
Maffei, Francisco H. A. [UNESP]
Oliva, Maria Luiza V.
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidade Federal de São Paulo (UNIFESP)
Charitable Assoc Blood Collect COLSAN
Case Western Reserve Univ
Univ Hosp Cleveland
NCI
Universidade Estadual Paulista (Unesp)
dc.contributor.author.fl_str_mv Ottaiano, Tatiana F.
Andrade, Sheila S.
Oliveira, Cleide de
Silva, Mariana C. C.
Buri, Marcus V.
Juliano, Maria A.
Girao, Manoel J. B. C.
Sampaio, Misako U.
Schmaier, Alvin H.
Wlodawer, Alexander
Maffei, Francisco H. A. [UNESP]
Oliva, Maria Luiza V.
dc.subject.por.fl_str_mv ADP
Integrin alphallbbeta3
Plasma kallikrein
Platelet aggregation
topic ADP
Integrin alphallbbeta3
Plasma kallikrein
Platelet aggregation
description Human plasma kallikrein (huPK) potentiates platelet responses to subthreshold doses of ADP, although huPK itself, does not induce platelet aggregation. In the present investigation, we observe that huPK pretreatment of platelets potentiates ADP-induced platelet activation by prior proteolysis of the G-protein -coupled receptor PAR-1. The potentiation of ADP-induced platelet activation by huPK is mediated by the integrin alpha(IIb)beta(3) through interactions with the KGD/KGE sequence motif in huPK. Integrin alpha(IIb)beta(3) is a cofactor for huPK binding to platelets to support PAR-1 hydrolysis that contributes to activation of the ADP signaling pathway. This activation pathway leads to phosphorylation of Src, AktS(473), ERK1/2, and p38 MAPK, and to Cat(2+) release. The effect of huPK is blocked by specific antagonists of PAR-1 (SCH 19197) and alpha(IIb)beta(3) (abciximab) and by synthetic peptides comprising the KGD and KGE sequence motifs of huPK. Further, recombinant plasma kallikrein inhibitor, rBbKI, also blocks this entire mechanism. These results suggest a new function for huPK. Formation of plasma kallikrein lowers the threshold for ADP-induced platelet activation. The present observations are consistent with the notion that plasma kallikrein promotes vascular disease and thrombosis in the intravascular compartment and its inhibition may ameliorate cardiovascular disease and thrombosis. (C) 2017 Elsevier B.V. and Societe Francaise de Biochimie et Biologie Moleculaire (SFBBM). All rights reserved.
publishDate 2017
dc.date.none.fl_str_mv 2017-04-01
2018-11-26T17:21:13Z
2018-11-26T17:21:13Z
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.uri.fl_str_mv http://dx.doi.org/10.1016/j.biochi.2017.01.010
Biochimie. Paris: Elsevier France-editions Scientifiques Medicales Elsevier, v. 135, p. 72-81, 2017.
0300-9084
http://hdl.handle.net/11449/162628
10.1016/j.biochi.2017.01.010
WOS:000397694600009
WOS000397694600009.pdf
url http://dx.doi.org/10.1016/j.biochi.2017.01.010
http://hdl.handle.net/11449/162628
identifier_str_mv Biochimie. Paris: Elsevier France-editions Scientifiques Medicales Elsevier, v. 135, p. 72-81, 2017.
0300-9084
10.1016/j.biochi.2017.01.010
WOS:000397694600009
WOS000397694600009.pdf
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Biochimie
1,554
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 72-81
application/pdf
dc.publisher.none.fl_str_mv Elsevier B.V.
publisher.none.fl_str_mv Elsevier B.V.
dc.source.none.fl_str_mv Web of Science
reponame:Repositório Institucional da UNESP
instname:Universidade Estadual Paulista (UNESP)
instacron:UNESP
instname_str Universidade Estadual Paulista (UNESP)
instacron_str UNESP
institution UNESP
reponame_str Repositório Institucional da UNESP
collection Repositório Institucional da UNESP
repository.name.fl_str_mv Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)
repository.mail.fl_str_mv
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