Plasmodium falciparum proteases hydrolyze plasminogen, generating angiostatin-like fragments

dc.contributor.authorMelo, Pollyana Maria Saud [UNIFESP]
dc.contributor.authorBagnaresi, Piero [UNIFESP]
dc.contributor.authorPaschoalin, Thaysa [UNIFESP]
dc.contributor.authorHirata, Izaura Yoshico [UNIFESP]
dc.contributor.authorGazarini, Marcos Leoni [UNIFESP]
dc.contributor.authorCarmona, Adriana Karaoglanovic [UNIFESP]
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.date.accessioned2016-01-24T14:35:03Z
dc.date.available2016-01-24T14:35:03Z
dc.date.issued2014-01-01
dc.description.abstractMalaria is a disease caused by Plasmodium parasites and remains one of the most prevalent and persistent maladies, affecting hundreds of millions of people. in the present work, we evaluated the capability of Plasmodium falciparum proteases to hydrolyze the multifunctional protein plasminogen, which is implicated in angiogenesis and coagulation processes by the generation of angiostatin and plasmin, respectively. Using fluorescence microscopy, we visualized the internalization of FITC-labeled plasminogen in erythrocytes infected by P. falciparum and showed that the parasites are able to hydrolyze the protein. the cleavage of plasminogen by the P. falciparum proteases was also observed by SDS-PAGE, followed by immunoblotting with anti-angiostatin antibody. N-terminal sequencing of the main generated fragments indicated that they are comprised in the five plasminogen kringle domains, suggesting as being angiostatin-like peptides. This assumption was reinforced by the demonstration that the products of plasminogen processing mimic angiostatin functions, including the capability to inhibit angiogenesis and to stimulate calcium response in endothelial cells in vitro. However, no plasmin activity was detected after plasminogen hydrolysis by P. falciparum. Nonetheless, exogenous tissue plasminogen activator (tPA) activated plasmin in infected erythrocytes, suggesting that the uptake of plasminogen by P. falciparum may be modulated by the vertebrate host. Taken together, the data presented here provide evidence for the processing of host plasminogen by malaria parasites to generate active fragments that may modulate host physiology events during malaria infection. (C) 2014 Elsevier B.V. All rights reserved.en
dc.description.affiliationUniversidade Federal de São Paulo, Dept Biofis, BR-04039032 São Paulo, Brazil
dc.description.affiliationUniversidade Federal de São Paulo, Dept Microbiol Imunol & Parasitol, BR-04023062 São Paulo, Brazil
dc.description.affiliationUniversidade Federal de São Paulo, Dept Biociencias, BR-11060001 Santos, SP, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Dept Biofis, BR-04039032 São Paulo, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Dept Microbiol Imunol & Parasitol, BR-04023062 São Paulo, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Dept Biociencias, BR-11060001 Santos, SP, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipIDFAPESP: 2009/545989-9
dc.description.sponsorshipIDFAPESP: 2009/11261-4
dc.description.sponsorshipIDFAPESP: 2009/53840-0
dc.description.sponsorshipIDFAPESP: 2010/51423-0
dc.description.sponsorshipIDFAPESP: 2012/50475-2
dc.format.extent45-54
dc.identifierhttps://dx.doi.org/10.1016/j.molbiopara.2014.01.004
dc.identifier.citationMolecular and Biochemical Parasitology. Amsterdam: Elsevier B.V., v. 193, n. 1, p. 45-54, 2014.
dc.identifier.doi10.1016/j.molbiopara.2014.01.004
dc.identifier.issn0166-6851
dc.identifier.urihttps://repositorio.unifesp.br/handle/11600/37244
dc.identifier.wosWOS:000335427800007
dc.language.isoeng
dc.publisherElsevier B.V.
dc.relation.ispartofMolecular and Biochemical Parasitology
dc.rightsinfo:eu-repo/semantics/restrictedAccess
dc.rights.licensehttp://www.elsevier.com/about/open-access/open-access-policies/article-posting-policy
dc.subjectMalariaen
dc.subjectPlasmodiumen
dc.subjectPlasminogenen
dc.subjectAngiostatinen
dc.subjectPlasminen
dc.titlePlasmodium falciparum proteases hydrolyze plasminogen, generating angiostatin-like fragmentsen
dc.typeinfo:eu-repo/semantics/article
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