Evaluation of the importance of glycolytic pathway, oxidative stress and fatty acid synthesis in the infection of cardiomyocytes by Trypanosoma cruzi

• Grant number: 16/25845-1
• Support Opportunities: Scholarships in Brazil - Master
• Start date: September 01, 2017
• End date: July 31, 2019
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Alexandre da Costa Pereira
• Grantee: Juliana Morais Alvim
• Host Institution: Instituto do Coração Professor Euryclides de Jesus Zerbini (INCOR). Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

Chagas Disease remains an important cause of mortality due to cardiac events such as dilated cardiomyopathy and arrhythmias, these patients presenting a worse prognosis compared to patients with other cardiomyopathies. Nowadays knowledge about Chagas disease is insufficient to inhibit infection and control the development of the disease in the chronic phase. Data from the literature and our group demonstrated that several intracellular pathways are altered during cardiomyocytes infection by parasites, and the glycolytic, fatty acid metabolism and oxidative stress generation pathways appear to be activated during the infection process. Studies about the role of these pathways during infection and replication of the parasite can help to achieve a better understanding of the process and suggest therapeutic targets for disease control. The present study aims to evaluate the effect of the modulation of these pathways on the infection rate and on the gene expression and metabolomic profile during the infection. Cardiomyocytes derived from iPS will be infected with T. cruzi in 2-deoxyglucose-containing medium for glycolytic pathway modulation; Resveratrol, for modulation of oxidative stress and estrogens for modulation of fatty acid synthesis. The infection rates will be analyzed by immunofluorescence, the transcriptional profile will be monitored using RNAseq and the metabolomic profile through metabolomic assay. (AU)

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)

ALVIM, JULIANA M.; VENTURINI, GABRIELA; OLIVEIRA, THEO G. M.; SEIDMAN, JONATHAN G.; SEIDMAN, CHRISTINE E.; KRIEGER, JOSE E.; PEREIRA, ALEXANDRE C.. mTOR signaling inhibition decreases lysosome migration and impairs the success of Trypanosoma cruzi infection and replication in cardiomyocytes. Acta Tropica, v. 240, p. 9-pg., 2023-02-01. (17/13706-0, 16/25845-1, 19/11821-1)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

ALVIM, Juliana Morais. Effects of rapamycin on the human cardiomyocytes infection by Trypanosoma cruzi. 2019. Master's Dissertation - Universidade de São Paulo (USP). Faculdade de Medicina (FM/SBD) São Paulo.