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Functional evaluation of fatty acid-binding protein 4 (FABP4) and modulation by PPAR-gamma in Leishmania amazonensis

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Author(s):
Amanda de Barros Piffer
Total Authors: 1
Document type: Master's Dissertation
Press: Campinas, SP.
Institution: Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia
Defense date:
Examining board members:
Danilo Ciccone Miguel; Marcelo Bispo de Jesus; Mauro Javier Cortez Veliz
Advisor: Danilo Ciccone Miguel
Abstract

Amastigote forms of the genus Leishmania parasitize cells of the mononuclear phagocytic system dividing by binary fission within parasitophorous vacuoles. Currently, little is understood about the molecular mechanisms that control Leishmania metabolism in these organelles, both from macromolecule biosynthesis and the host cell metabolic control by the parasite aspects. Preliminary transcriptomic analysis studies showed an increase in FABP4 (fatty acid-binding protein 4) transcripts in macrophages infected with L. (L.) amazonensis for 48h. Because they are small intracellular proteins, FABPs access the cell nucleus under certain physiological conditions carrying fatty acids to transcription factors, such as peroxisome proliferator-activated receptors (e.g. PPAR-gamma). FABP type 4 is responsible for the transport of fatty acids to different cell compartments in both macrophages and adipocytes. Based on the biological properties described for FABP4, in addition to the fact that amastigote forms depend on fatty acid metabolism for amino acid biosynthesis, it is speculated that macrophagic FABP4 may play an important role in lipid homeostasis in the infected cell during the infection process by Leishmania. Thus, it was intended to investigate in this project the role of FABP4 in in vitro infection assays using macrophages in the presence of FABP4-specific inhibitor as well as with reduced expression of the FABP4 gene, via RNA interference. In addition, the participation of PPAR-gamma, which is known to interact with FABP4, was investigated L. (L.) amazonensis infections in vitro. With different techniques it was possible to validate the influence of both proteins on the establishment and survival of these parasites. In vivo studies were conducted to evaluate the role of PPAR-gamma in the lesion evolution caused by L. (L.) amazonensis in C57BL/6 mice knocked out for this protein, suggesting that with reduced parasite inoculation, there is a delay during lesion progression between the 6th and 8th week in the absence of PPAR-gamma. Briefly, although it was not possible to fully elucidate the relationship between such cellular components during this event, we confirm that changes in this balance interferes with the infectious capacity of L. (L.) amazonensis. Thus, both FABP4 and PPAR-gamma are relatively important during the in vitro infection process (AU)

FAPESP's process: 17/06542-0 - Functional evaluation of fatty acid binding protein 4 (FABP4) and PPAR-gamma modulation in Leishmania amazonensis
Grantee:Amanda de Barros Piffer
Support Opportunities: Scholarships in Brazil - Master