Participation of phosphorylation and calcium homeostasis in intracellular proteolytic activity modulation in Plasmodium chabaudi

Abstract

Malaria is an aggressive disease, responsible for many deaths each year. The Plasmodium, parasite responsible for this pathology has great variability in its gene expression and it's responsible for changes in the characteristics of proteins. These changes are resulted from mutations and can lead the parasites to increased resistance to antimalarial drugs. The proteolytic activity of Plasmodium is a crucial process, because this are involved in primordial processes in the metabolism of the parasite, like the invasion and egress of erythrocytes, hemoglobin degradation for the acquisition of amino acids, among others. As in other eukaryotic cells, cellular events are regulated by the second messenger calcium, which participates in the modulation of various cellular events such as cell division and differentiation, but studies are still lacking the specificity of proteases regulation by changes in intracellular calcium in malaria parasites. Another important element in intracellular signaling is the phosphorylation of proteins, which can also be an important modulator of protease activity, yet little explored in Plasmodium. The utilization of selective inhibitors of peptidases has been used as a therapeutic target for fungal infections, parasitic and bacterial infections. Peptidases are considered important targets for antimalarials and are necessary studies showing proteolytic activity involvement in regulation of these proteins and possible changes in affinity to inhibitors. The project aims, through spectrofluorometer and confocal microscopy assays the measurements of intracellular proteolytic activity in Plasmodium chabaudi, associated with signaling mechanisms and cell biology to provide new information on the regulation of these enzymes. (AU)