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Nitric oxide cell signaling during Trypanosoma cruzi differentiation and adhesion to extracellular matrix

Grant number: 12/05621-0
Support Opportunities:Scholarships in Brazil - Post-Doctorate
Effective date (Start): July 01, 2012
Effective date (End): September 30, 2014
Field of knowledge:Biological Sciences - Biochemistry - Biochemistry of Microorganisms
Principal Investigator:Maria Julia Manso Alves
Grantee:Chrislaine Oliveira Soares
Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Invasion of mammalian cells by T. cruzi trypomastigotes is a multi-step and complex process involving several adhesion molecules, signaling events and proteolytic activities. Although the mechanism of trypomastigotes interaction with mammalian cells has been intensively studied, a final and integrated picture of the signal transduction mechanisms involved remains to be elucidated. Members of the gp85/trans-sialidase glycoprotein family coating the surface of trypomastigotes are essential to parasite recognition and adhesion to the host cell. The binding to extracellular matrix (ECM) components of the host cell triggers signaling cascades, culminating in changes in the phosphorylation pattern of a variety of trypomastigotes' proteins. Currently, our group is interested in verify the role of nitric oxide signaling cascades during invasion and differentiation of the parasite. Recently, it was shown that T. cruzi produces NO via TcNOS, which presents similar characteristics to mammalian NOS, and able to induce cGMP production. Our interests rely mainly on the post-translational modifications mediated by NO. According to the literature, nitration of tyrosine residues or S-nitrosylation modulates the biological activity of a large diversity of proteins by interfering in its phosphorylation, ubiquination, sumoylation levels and other post-translational modifications. Therefore, this proposal research project aims to clarify the relation of NO on T. cruzi invasion and in vitro differentiation of trypomastigotes to amastigotes. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
PEREIRA, MILTON; SOARES, CHRISLAINE; BAPTISTA CANUTO, GISELE ANDRE; MAGGI TAVARES, MARINA FRANCO; COLLI, WALTER; ALVES, MARIA JULIA M.. Down Regulation of NO Signaling in Trypanosoma cruzi upon Parasite-Extracellular Matrix Interaction: Changes in Protein Modification by Nitrosylation and Nitration. PLoS Neglected Tropical Diseases, v. 9, n. 4, . (12/03887-3, 12/05621-0)

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