Intracellular proteolysis of kininogen by malaria parasites promotes release of active kinins

Show simple item record

dc.contributor.author Bagnaresi, Piero [UNIFESP]
dc.contributor.author Barros, Nilana Meza Tenório [UNIFESP]
dc.contributor.author Assis, Diego M. [UNIFESP]
dc.contributor.author Melo, Pollyana M. S. [UNIFESP]
dc.contributor.author Fonseca, Raphael G. [UNIFESP]
dc.contributor.author Juliano, Maria Aparecida [UNIFESP]
dc.contributor.author Pesquero, João Bosco [UNIFESP]
dc.contributor.author Juliano, Luiz [UNIFESP]
dc.contributor.author Rosenthal, Philip J.
dc.contributor.author Carmona, Adriana Karaoglanovic [UNIFESP]
dc.contributor.author Gazarini, Marcos Leoni [UNIFESP]
dc.date.accessioned 2016-01-24T14:27:14Z
dc.date.available 2016-01-24T14:27:14Z
dc.date.issued 2012-05-07
dc.identifier http://dx.doi.org/10.1186/1475-2875-11-156
dc.identifier.citation Malaria Journal. London: Biomed Central Ltd, v. 11, 10 p., 2012.
dc.identifier.issn 1475-2875
dc.identifier.uri http://repositorio.unifesp.br/handle/11600/34889
dc.description.abstract Background: the malaria burden remains a major public health concern, especially in sub-Saharan Africa. the complex biology of Plasmodium, the apicomplexan parasite responsible for this disease, challenges efforts to develop new strategies to control the disease. Proteolysis is a fundamental process in the metabolism of malaria parasites, but roles for proteases in generating vasoactive peptides have not previously been explored.Results: in the present work, it was demonstrated by mass spectrometry analysis that Plasmodium parasites (Plasmodium chabaudi and Plasmodium falciparum) internalize and process plasma kininogen, thereby releasing vasoactive kinins (Lys-BK, BK and des-Arg(9)-BK) that may mediate haemodynamic alterations during acute malaria. in addition, it was demonstrated that the P. falciparum cysteine proteases falcipain-2 and falcipain-3 generated kinins after incubation with human kininogen, suggesting that these enzymes have an important role in this process. the biologic activity of peptides released by Plasmodium parasites was observed by measuring ileum contraction and activation of kinin receptors (B1 and B2) in HUVEC cells; the peptides elicited an increase in intracellular calcium, measured by Fluo-3 AM fluorescence. This effect was suppressed by the specific receptor antagonists Des-Arg(9)[Leu(8)]-BK and HOE-140.Conclusions: in previously undescribed means of modulating host physiology, it was demonstrated that malaria parasites can generate active kinins by proteolysis of plasma kininogen. en
dc.description.sponsorship Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorship Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.description.sponsorship FADA (UNIFESP)
dc.format.extent 10
dc.language.iso eng
dc.publisher Biomed Central Ltd
dc.relation.ispartof Malaria Journal
dc.rights Acesso aberto
dc.title Intracellular proteolysis of kininogen by malaria parasites promotes release of active kinins en
dc.type Artigo
dc.contributor.institution Universidade Federal de São Paulo (UNIFESP)
dc.contributor.institution Univ Calif San Francisco
dc.description.affiliation Universidade Federal de São Paulo, Dept Biofis, BR-04039032 São Paulo, Brazil
dc.description.affiliation Universidade Federal de São Paulo, Dept Ciencias Exatas & Terra, BR-09972270 São Paulo, Brazil
dc.description.affiliation Univ Calif San Francisco, San Francisco Gen Hosp, Dept Med, San Francisco, CA 94110 USA
dc.description.affiliation Universidade Federal de São Paulo, Dept Biociencias, BR-11060001 São Paulo, Brazil
dc.description.affiliationUnifesp Universidade Federal de São Paulo, Dept Biofis, BR-04039032 São Paulo, Brazil
dc.description.affiliationUnifesp Universidade Federal de São Paulo, Dept Ciencias Exatas & Terra, BR-09972270 São Paulo, Brazil
dc.description.affiliationUnifesp Universidade Federal de São Paulo, Dept Biociencias, BR-11060001 São Paulo, Brazil
dc.description.sponsorshipID FAPESP: 09/54598-9
dc.identifier.file WOS000307020400001.pdf
dc.identifier.doi 10.1186/1475-2875-11-156
dc.description.source Web of Science
dc.identifier.wos WOS:000307020400001



File

Name: WOS000307020400001.pdf
Size: 1.705Mb
Format: PDF
Description:
Open file

This item appears in the following Collection(s)

Show simple item record

Search


Browse

Statistics

My Account