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Doctoral Thesis
DOI
https://doi.org/10.11606/T.42.2013.tde-20032014-174955
Document
Author
Full name
Eduardo Alves dos Santos
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2013
Supervisor
Committee
Garcia, Celia Regina da Silva (President)
Marinho, Claudio Romero Farias
Oliveira, Pedro Lagerblad de
Teixeira, Santuza Maria Ribeiro
Wrenger, Carsten
Title in Portuguese
Papel do IP3 na transdução de sinal e função da heme oxigenase em Plasmodium falciparum.
Keywords in Portuguese
Plasmodium
Antimaláricos
Biliverdina
Melatonina
Metaloprotoporfirinas
Transdução de sinal celular
Abstract in Portuguese
Demonstramos que o P. falciparum dentro do eritrócito é capaz de usar a via de sinalização celular dependente do inositol trifosfato (IP3). Investigamos os estoques de Ca2+ intracelular sensíveis ao IP3 neste parasita e a sensibilidade ao IP3 em diferentes estágios no ciclo intraeritrocítico. Demonstramos que o hormônio melatonina é capaz de aumentar a concentração de IP3 neste parasita. Com o uso de uma coluna de afinidade ao IP3 tentamos encontrar proteínas candidatas ao receptor de IP3 em P. falciparum. Este trabalho também estuda a enzima heme oxigenade de P. falciparum (PfHO). Testamos a capacidade desta enzima em converter biliverdina (BV) em bilirubina (BR), a modulação desta atividade na presença de diversas metaloprotoporfirinas e o potencial destes compostos como antimaláricos. Reportamos que a biliverdina é capaz de modular o ciclo intraeritrocítico de P. falciparum e apresentamos a proteína enolase de P. falciparum como candidato ao sensor de BV neste parasita.
Title in English
IP3 role in signal transduction and function of heme oxygenase in Plasmodium falciparum.
Keywords in English
Plasmodium
Antimalarials
Biliverdin
Cellular signal transduction
Melatonin
Metallo-protoporphyrins
Abstract in English
We demonstrate that P. falciparum within the erythrocyte is able to use the cellular signaling pathway dependent on inositol triphosphate (IP3). We investigated the intracellular Ca2+ stores sensitive to IP3 and explore parasite sensitivity to IP3 at different stages in the intraerythrocytic cycle. We demonstrate that melatonin hormone is capable of increasing the IP3 concentration on this parasite. Using an IP3 affinity column, we tried to find candidate proteins for IP3 receptor in P. falciparum. This work also studies the enzyme P. falciparum heme oxygenase (PfHO). We tested the ability of this enzyme to convert biliverdin (BV) in bilirubin (BR), the modulation of this activity in the presence of various metalloprotoporphyrins and the potential of these compounds as antimalarials. We reported that biliverdin is capable of modulating the intraerythrocytic cycle of P. falciparum and present P. falciparum enolase as candidate for BV sensor on this parasite.
 
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Publishing Date
2014-03-29
 
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