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ALMEIDA. FCS. Plasmodium falciparum factors involved in eIF2α phosphorylation in response to melatonin. 2015. 90 p. [Masters thesis (Parasitology)]. São Paulo: Instituto de Ciências Biomédicas, Universidade de São Paulo; 2015. Malaria is caused by the Apicomplexan parasite Plasmodium and is considered one of the most lethal infeccious diseases that affect human beings. The parasite has a complex life cycle, in which the intraerithrocytic phase is responsible for the pathogenesis and induces several biochemical and strucutural changes within host cell. Although some aspects of the biology of the parasite are still not clear, it is known that the intraerythrocytic cycle regulation is critical for understanding the Plasmodium life cycle. Unraveling the mechanisms of signal transduction pathways engendered by the parasite is a fundamental question, considering the resistance to artemisinin and the urgency for development of new strategies to combat the disease. Melatonin modulates the intraerythrocytic phase of P. falciparum e P. chabaudi promoting synchronization. Although, the signal transduction mechanism induced by melatonin is partially characterized, the role of calcium AMPc and PKA is now recognized. Since post translational modifications actively participate in signal transduction pathways, we have searched for the role of phosphorylation in this process as in addition of PKA, the PfPK7 kinase is also essential the melatonin signal transduction. In eukaryotes the control of gene expression via protein phosphorylation kinases can interfere with gene transcription and translation. The eIF2α factor is able to activate translation of mRNAs in response to unfavorable situations. In silico analyzes showed that Plasmodium falciparum genome encodes three protein kinases that able to phosphorylate the eIF2α and thus, modulate eIF2α activity: PfeIK1, and PfeIK2 PfPK4. In this work, we have investigated the role of PfeIK1 in melatonin signal transduction using transgenic parasite (unable to express PfeIK1). Futhermore, we have also analysed the impact of heme and biliverdin, involved in heam metabolism in Plasmodium on their ability to phosphorylate eIF2α. Our results suggest that the mechanism of phosphorylation and dephosphorylation of eIF2α may be relevant to the response of the parasite to the treatment with haem or biliverdin, placing this factor as an important modulator of parasite cell cycle. On the other hand, we could not observed an increase of phosphorylation of eIF2α in comparison to what was observed under basal conditions. In conclusion, PfeIK1, PfPK7 and PKA are key kinases for the development of the parasite during intraerythrocytic cycle.

Fatores de <i>Plasmodium falciparum</i> envolvidos na fosforilação de eIF2&#945; em resposta a melatonina.

Fatores de <i>Plasmodium falciparum</i> envolvidos na fosforilação de eIF2α em resposta a melatonina.