FRET peptides reveal differential proteolytic activation in intraerythrocytic stages of the malaria parasites Plasmodium berghei and Plasmodium yoelii

FRET peptides reveal differential proteolytic activation in intraerythrocytic stages of the malaria parasites Plasmodium berghei and Plasmodium yoelii

Author Cruz, Laura Nogueira da Google Scholar
Alves, Eduardo Google Scholar
Leal, Monica Teixeira Google Scholar
Juliano, Maria Aparecida Autor UNIFESP Google Scholar
Rosenthal, Philip J. Google Scholar
Juliano, Luiz Autor UNIFESP Google Scholar
Garcia, Célia Regina da Silva Google Scholar
Institution Universidade de São Paulo (USP)
Universidade Federal de São Paulo (UNIFESP)
Univ Calif San Francisco
Abstract Malaria is still a major health problem in developing countries. It is caused by the protist parasite Plasmodium, in which proteases are activated during the cell cycle. Ca(2+) is a ubiquitous signalling ion that appears to regulate protease activity through changes in its intracellular concentration. Proteases are crucial to Plasmodium development, but the role of Ca(2+) in their activity is not fully understood. Here we investigated the role of Ca(2+) in protease modulation among rodent Plasmodium spp. Using fluorescence resonance energy transfer (FRET) peptides, we verified protease activity elicited by Ca(2+) from the endoplasmatic reticulum (ER) after stimulation with thapsigargin (a sarco/endoplasmatic reticulum Ca(2+)-ATPase (SERCA) inhibitor) and from acidic compartments by stimulation with nigericin (a K(+)/H(+) exchanger) or monensin (a Na(+)/H(+) exchanger). Intracellular (BAPTA/AM) and extracellular (EGTA) Ca(2+) chelators were used to investigate the role played by Ca(2+) in protease activation. in Plasmodium berghei both EGTA and BAPTA blocked protease activation, whilst in Plasmodium yoelii these compounds caused protease activation. the effects of protease inhibitors on thapsigargin-induced proteolysis also differed between the species. Pepstatin A and phenylmethylsulphonyl fluoride (PMSF) increased thapsigargin-induced proteolysis in P. berghei but decreased it in P. yoelii. Conversely. E64 reduced proteolysis in P. berghei but stimulated it in P. yoelii. the data point out key differences in proteolytic responses to Ca(2+) between species of Plasmodium. (C) 2011 Australian Society for Parasitology Inc. Published by Elsevier B.V. All rights reserved.
Keywords Malaria
Plasmodium berghei
Plasmodium yoelii
Protease activity
Ca(2+) modulation
FRET
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Date 2011-03-01
Published in International Journal for Parasitology. Oxford: Elsevier B.V., v. 41, n. 3-4, p. 363-372, 2011.
ISSN 0020-7519 (Sherpa/Romeo, impact factor)
Publisher Elsevier B.V.
Extent 363-372
Origin http://dx.doi.org/10.1016/j.ijpara.2010.10.009
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000288736700012
URI http://repositorio.unifesp.br/handle/11600/33483

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