Analysis of the effect of peptides on the activity of metacaspase and apoptosis in Leishmania (L.) amazonensis

Abstract

Leishmaniasis is an important human disease caused by various species of Leishmania, transmitted by sandflies. In Brazil Leishmania Leishmania amazonensis is one of the important species causing the disease, which can present different clinical forms, most commonly localized cutaneous leishmaniasis (LCL) and more rarely diffuse cutaneous leishmaniasis (LCD).Apoptosis is a type of programmed cell death described in multicellular organisms, which is usually followed by removal of such cells without the production of inflammatory mediators. Characteristics similar to apoptosis were observed in parasitic protozoa, including Leishmania. These parasites probably utilize this process to decrease the inflammatory response in the vertebrate host, increasing infection. This type of cell death relies on intracellular proteases such as caspases in metazoans and metacaspases (MCAs) in protozoa, plants and fungi. In a project conducted in our laboratory fifteen MCA peptide ligands were identified that can provide information on the regulation and control of the activity of this enzyme, and on its relationship to cell death in Leishmania. As a continuation of this project, we will analyze the effect of these fifteen peptide ligands of Leishmania (L.) amazonensis MCA in the activity of this enzyme, in parasite growth and in cell death induced or not by heat shock or treatment with hydrogen peroxide. By integrating the results that we will obtain on cell viability, apoptosis and activity of MCA, we hope to understand how the modulation of MCA activity by the peptides affects parasite death.