Extracellular ATP triggers proteolysis and cytosolic Ca2+ rise in Plasmodium berghei and Plasmodium yoelii malaria parasites

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dc.contributor.author Cruz, Laura Nogueira
dc.contributor.author Juliano, Maria Aparecida [UNIFESP]
dc.contributor.author Budu, Alexandre
dc.contributor.author Juliano, Luiz [UNIFESP]
dc.contributor.author Holder, Anthony A.
dc.contributor.author Blackman, Michael J.
dc.contributor.author Garcia, Celia R. S.
dc.date.accessioned 2016-01-24T14:26:58Z
dc.date.available 2016-01-24T14:26:58Z
dc.date.issued 2012-03-15
dc.identifier http://dx.doi.org/10.1186/1475-2875-11-69
dc.identifier.citation Malaria Journal. London: Biomed Central Ltd, v. 11, 11 p., 2012.
dc.identifier.issn 1475-2875
dc.identifier.uri http://repositorio.unifesp.br/handle/11600/34713
dc.description.abstract Background: Plasmodium has a complex cell biology and it is essential to dissect the cell-signalling pathways underlying its survival within the host.Methods: Using the fluorescence resonance energy transfer (FRET) peptide substrate Abz-AIKFFARQ-EDDnp and Fluo4/AM, the effects of extracellular ATP on triggering proteolysis and Ca2+ signalling in Plasmodium berghei and Plasmodium yoelii malaria parasites were investigated.Results: the protease activity was blocked in the presence of the purinergic receptor blockers suramin (50 mu M) and PPADS (50 mu M) or the extracellular and intracellular calcium chelators EGTA (5 mM) and BAPTA/AM (25, 100, 200 and 500 mu M), respectively for P. yoelii and P. berghei. Addition of ATP (50, 70, 200 and 250 mu M) to isolated parasites previously loaded with Fluo4/AM in a Ca2+-containing medium led to an increase in cytosolic calcium. This rise was blocked by pre-incubating the parasites with either purinergic antagonists PPADS (50 mu M), TNP-ATP (50 mu M) or the purinergic blockers KN-62 (10 mu M) and Ip5I (10 mu M). Incubating P. berghei infected cells with KN-62 (200 mu M) resulted in a changed profile of merozoite surface protein 1 (MSP1) processing as revealed by western blot assays. Moreover incubating P. berghei for 17 h with KN-62 (10 mu M) led to an increase in rings forms (82% +/- 4, n = 11) and a decrease in trophozoite forms (18% +/- 4, n = 11).Conclusions: the data clearly show that purinergic signalling modulates P. berghei protease(s) activity and that MSP1 is one target in this pathway. 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 UK Medical Research Council
dc.description.sponsorship EU through the Network of Excellence EviMalaR
dc.format.extent 11
dc.language.iso eng
dc.publisher Biomed Central Ltd
dc.relation.ispartof Malaria Journal
dc.rights Acesso aberto
dc.subject ATP en
dc.subject Purinergic receptor en
dc.subject Malaria en
dc.subject Plasmodium berghei en
dc.subject Plasmodium yoelii en
dc.subject Protease activity en
dc.subject Calcium modulation en
dc.subject Merozoite surface protein 1 en
dc.title Extracellular ATP triggers proteolysis and cytosolic Ca2+ rise in Plasmodium berghei and Plasmodium yoelii malaria parasites en
dc.type Artigo
dc.contributor.institution Universidade de São Paulo (USP)
dc.contributor.institution Universidade Federal de São Paulo (UNIFESP)
dc.contributor.institution MRC Natl Inst Med Res
dc.description.affiliation Univ São Paulo, Dept Physiol, Inst Biociencias, BR-05508900 São Paulo, SP, Brazil
dc.description.affiliation Universidade Federal de São Paulo, Escola Paulista Med, Dept Biophys, BR-04044020 São Paulo, SP, Brazil
dc.description.affiliation MRC Natl Inst Med Res, Div Parasitol, London NW7 1AA, England
dc.description.affiliation Univ São Paulo, Inst Ciencias Biomed, Dept Parasitol, BR-05508900 São Paulo, SP, Brazil
dc.description.affiliationUnifesp Universidade Federal de São Paulo, Escola Paulista Med, Dept Biophys, BR-04044020 São Paulo, SP, Brazil
dc.description.sponsorshipID UK Medical Research Council: U117532067
dc.description.sponsorshipID UK Medical Research Council: U117532063
dc.description.sponsorshipID EU through the Network of Excellence EviMalaR: Health-2009-2.3.2-1-242095
dc.identifier.file WOS000304544700001.pdf
dc.identifier.doi 10.1186/1475-2875-11-69
dc.description.source Web of Science
dc.identifier.wos WOS:000304544700001



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