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

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

Author Bagnaresi, Piero Autor UNIFESP Google Scholar
Barros, Nilana Meza Tenório Autor UNIFESP Google Scholar
Assis, Diego M. Autor UNIFESP Google Scholar
Melo, Pollyana M. S. Autor UNIFESP Google Scholar
Fonseca, Raphael G. Autor UNIFESP Google Scholar
Juliano, Maria Aparecida Autor UNIFESP Google Scholar
Pesquero, João Bosco Autor UNIFESP Google Scholar
Juliano, Luiz Autor UNIFESP Google Scholar
Rosenthal, Philip J. Google Scholar
Carmona, Adriana Karaoglanovic Autor UNIFESP Google Scholar
Gazarini, Marcos Leoni Autor UNIFESP Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Univ Calif San Francisco
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.
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Grant number FAPESP: 09/54598-9
Date 2012-05-07
Published in Malaria Journal. London: Biomed Central Ltd, v. 11, 10 p., 2012.
ISSN 1475-2875 (Sherpa/Romeo, impact factor)
Publisher Biomed Central Ltd
Extent 10
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000307020400001

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