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Doctoral Thesis
DOI
https://doi.org/10.11606/T.42.2010.tde-10082010-143652
Document
Author
Full name
Laura Nogueira da Cruz
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2010
Supervisor
Committee
Garcia, Celia Regina da Silva (President)
Barcinski, Marcello Andre
Silva, Aline Maria da
Teixeira, Marta Maria Geraldes
Ulrich, Alexander Henning
Title in Portuguese
Estudos de fisiologia comparativa de modelos de malária em roedor.
Keywords in Portuguese
Cálcio
Células eucarióticas
Citofisiologia
Doenças parasitárias
Malária
Receptores celulares
Abstract in Portuguese
Malária é um dos principais problemas de saúde nos países em desenvolvimento sendo o Plasmodium o agente etiológico da doença. Neste trabalho foi investigada a função do Ca2+ e da sinalização purinérgica na modulação proteolítica de Plasmodium. Utilizando peptídeos com apagamento intracelular de fluorescência (FRET) analisamos a atividade proteolítica ativada por Ca2+ liberado do retículo endoplasmático ou de compartimentos ácidos e investigamos as diferentes classes de proteases envolvidas. Utilizando-se P. berghei e P. yoelii verificou-se a importância do Ca2+ na modulação proteolítica além de diferenças fisiológicas nesta modulação dentre as espécies estudadas. Foram também investigados os efeitos de ATP, adenosina e GTP extracelular na proteólise e conclui-se que receptores purinérgicos estão envolvidos na habilidade do parasita ativar proteólise intracelular. Na terceira parte da tese foi estabelecido um modelo murino nocaute para analisar a relação Plasmodium-hospedeiro e propõem-se a interação do receptor InsP3R2 e a proteína PbRACK do parasita.
Title in English
Comparative physiology studies of rodent malaria models.
Keywords in English
Calcium
Cell receptors
Cytophysiology
Eukariotic cell
Malaria
Parasitology disease
Abstract in English
Malaria is a major health problem in developing countries Here we investigate the role of Ca2+ and purines in Plasmodium protease modulation. Using fluorescence resonance energy transfer (FRET) peptides, we verified protease activity elicited by Ca2+from endoplasmatic reticulum or acidic compartments and investigated the classes of affected proteases. Experiments in P. berghei and P. yoelii indicated a fundamental role for calcium in modulating proteolysis and points out key differences in proteolytic responses between Plasmodium species. We also investigated the effects of extracellular ATP, adenosine and GTP on triggering proteolysis. The data lead us to conclude that purinergic receptor is involved in the ability of the parasite to activate intracellular proteolysis by sensing external molecules. The third part of the thesis established a new murine knockout model to analyze Plasmodium-host signaling and suggest a possible interaction between InsP3R2 receptor and the PbRACK parasite protein.
 
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Publishing Date
2010-09-20
 
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