Influência da ck2 no processo de interação Leishmania donovani-macrófagos

• Autor(a) principal: Silva, Simone Sandy da
• Data de Publicação: 2012
• Tipo de documento: Dissertação
• Idioma: por
• Título da fonte: Biblioteca Digital de Teses e Dissertações da UERJ
• Texto Completo: http://www.bdtd.uerj.br/handle/1/14419
• topic: Leishmaniasis; Metacyclogenesis; Macrophage; Protein kinase 2(CK2); Inhibitor; Growth; Tetrabromoazamenzimodazol (TBB); Leishmaniose; Macrófagos; Proteínas Quinases; Leishmaniose; Metaciclogênese; Macrófagos; Proteína cinase 2(CK2); Inibidor; Crescimento; Tetrabromoazabenzimidazol (TBB); CNPQ::CIENCIAS BIOLOGICAS::PARASITOLOGIA::PROTOZOOLOGIA DE PARASITOS::PROTOZOOLOGIA PARASITARIA HUMANA

The genus Leishmania contains multiple species that are responsible for a group of diseases, leishmaniasis. Current estimates suggest that 12 million people are infected. When parasites enter a human host, they undergo metacyclogenesis and acquire the ability to interact with macrophages. This interaction activites signal transduction pathways inducing numerous biological activities, including protein kinase CK2. CK2 has been observed in all eukaryotic cells residing in the nucleus, the cytoplasm and on the cell surface. It appears to have an essential function and recognizes serine/threonine or tyrosine residues in target proteins for phosphorylation. In the present study, we demonstrate that the treatment of L. donovani promastigotes with TBB resulted in inhibition of cell growth and showed an irreversible mechanism of action, however was not able to induce apoptosis in L. donovani promastigotes. The pre-treatment of promastigotes and macrophages, as well as the addition of TBB during infection induced a significant reduction in the number of amastigotes per macrophages, possibly via the mechanism of programmed cell death showed by TUNEL technique. Treatment of macrophages with TBB did not induce the increase of nitric oxide. Immunofluorescence assays demonstrated the presence of CK2α distributed throughout the surface the promastigotes. Uninfected macrophages showed little to no CK2α. After initiating the interaction of parasites with macrophages, CK2α was observed distributed preferentially in the nucleus of macrophages. Job data suggest that CK2 is an important enzyme for the biological activity of Leishmania donovani, and its study important relevance to the discovery of new therapeutic targets.