title: Interaction between bradykinin B2 and Ang-(1-7) Mas receptors regulates erythrocyte invasion by Plasmodium falciparum.
abstract: The molecular mechanisms involved in erythrocyte invasion by malaria parasite are well understood, but the contribution of host components is not. We recently reported that Ang-(1-7) impairs the erythrocytic cycle of P. falciparum through Mas receptor-mediated reduction of protein kinase A (PKA) activity. The effects of bradykinin (BK), a peptide of the kallikrein-kinin system (KKS), can be potentiated by Ang-(1-7), or angiotensin-converting enzyme (ACE) inhibitors, such as captopril. We investigated the coordinated action between renin-angiotensin system (RAS) and KKS peptides in the erythrocyte invasion by P. falciparum.
  
  
  
  We used human erythrocytes infected with P. falciparum to assess the influence of RAS and KKS peptides in the invasion of new erythrocytes.
  
  
  
  The inhibitory effects of Ang-(1-7) were mimicked by captopril. 10(-8)M BK decreased new ring forms and this effect was sensitive to 10(-8)M HOE-140 and 10(-7)M A779, B2 and Mas receptor antagonists, respectively. However, DALBK, a B1 receptor blocker, had no effect. The inhibitory effect of Ang-(1-7) was reversed by HOE-140 and A779 at the same concentrations. Co-immunoprecipitation assay revealed an association between B2 and Mas receptors. BK also inhibited PKA activity, which was sensitive to both HOE-140 and A779.
  
  
  
  The results suggest that B2 and Mas receptors are mediators of Ang-(1-7) and BK inhibitory effects, through a cross-signaling pathway, possibly by the formation of a heterodimer.
  
  
  
  Our results describe new elements in host signaling that could be involved in parasite invasion during the erythrocyte cycle of P. falciparum.
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
authors.forename: Leandro de Souza
authors.initials: LS
authors.lastname: Silva
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
authors.forename: Diogo de Barros
authors.initials: DB
authors.lastname: Peruchetti
authors.affiliation: Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brazil; Rede Proteômica do Rio de Janeiro, RJ, Brazil.
authors.forename: Claudio Teixeira Ferreira-Da
authors.initials: CTF
authors.lastname: Silva
authors.affiliation: Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brazil; Rede Proteômica do Rio de Janeiro, RJ, Brazil.
authors.forename: André Teixeira
authors.initials: AT
authors.lastname: Ferreira-DaSilva
authors.affiliation: Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brazil; Rede Proteômica do Rio de Janeiro, RJ, Brazil.
authors.forename: Jonas
authors.initials: J
authors.lastname: Perales
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil; Instituto Nacional de Ciência e Tecnologia em Biologia e Bioimagem, Conselho Nacional de Desenvolvimento Científico e Tecnológico/MCT, Brazil.
authors.forename: Celso
authors.initials: C
authors.lastname: Caruso-Neves
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil; Instituto Nacional para Pesquisa Translacional em Saúde e Ambiente na Região Amazônica, Conselho Nacional de Desenvolvimento Científico e Tecnológico/MCT, Brazil. Electronic address: acacia@biof.ufrj.br.
authors.forename: Ana Acacia Sá
authors.initials: AAS
authors.lastname: Pinheiro
mesh_terms: D002478:Cells, Cultured; D004912:Erythrocytes / Q000469:parasitology*; D006801:Humans; D010963:Plasmodium falciparum / Q000378:metabolism / Q000472:pathogenicity*; D011485:Protein Binding; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D015800:Protozoan Proteins / Q000378:metabolism*; D043782:Receptor, Bradykinin B2 / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*
chemical_list: D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D015800:Protozoan Proteins; D043782:Receptor, Bradykinin B2; D043562:Receptors, G-Protein-Coupled
keywords: Angiotensin-(1–7); Bradykinin; Exchange protein activated by cAMP; Host-parasite interaction; Malaria