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Study of factors involved in lipid bodies formation induced by a Phospholipase A2, isolated from Bothrops asper snake venom: synthesis and metabolism of lipids

Grant number: 10/06345-1
Support Opportunities:Scholarships in Brazil - Doctorate
Effective date (Start): August 01, 2010
Effective date (End): November 30, 2013
Field of knowledge:Agronomical Sciences - Veterinary Medicine - Animal Pathology
Principal Investigator:Catarina de Fatima Pereira Teixeira
Grantee:Elbio Leiguez Junior
Host Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
Associated research grant:08/57898-0 - National Institute of Science and Technology on Toxins, AP.TEM
Associated scholarship(s):12/06730-8 - Study of the role of PLIN2 in inflammatory response induced by MT-III, a Phospholipase A2 isolated from Bothrops asper snake venom: lipid bodies biogenesis and release of inflammatory mediators, BE.EP.DR


The Bothrops venoms contain high concentrations of secreted phospholipase A2 (sPLA2), which have structural and functional homology with the mammalian PLA2s whose levels are increased in inflammatory diseases such as atherosclerosis. Recently we demonstrated that MT-III, a sPLA2, induced an increase in lipid bodies formation and expression of ADRP, a structural protein member of the PAT family which plays a key role in lipid body assembling, adipocyte differentiation and foam cells formation. However, the mechanisms involved in ADRP expression and lipid accumulation and synthesis induced by MT-III in macrophages remain unknown. Thus, this study will assess MT-III-effects I) on intracellular accumulation of triacylglycerol and cholesterol; II) on gene expression of enzymes involved in triacylglycerol and cholesterol synthesis; III) on activation and expression of PPAR-gama, PPAR-delta, CD36 receptors and IV) on activation and expression of transcription factor SREBP-2 in macrophages. The involvement of PPAR-gama, PPAR-delta and CD36 in lipid bodies formation and ADRP expression, induced by MT-III, in macrophages will also be assessed. In this sense, this work will promote a better understanding of the inflammatory reaction induced by Bothrops venoms. Moreover, this study will contribute to the understanding of actions of this family of enzymes in inflammatory processes and those related to lipid metabolism. Additionally, this study may reveal new therapeutics targets in diseases which lipid imbalance is a major factor. (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)
LEIGUEZ, ELBIO; GIANNOTTI, KARINA CRISTINA; MOREIRA, VANESSA; MATSUBARA, MARCIO HIDEKI; MARIA GUTIERREZ, JOSE; LOMONTE, BRUNO; PABLO RODRIGUEZ, JUAN; BALSINDE, JESUS; TEIXEIRA, CATARINA. Critical Role of TLR2 and MyD88 for Functional Response of Macrophages to a Group IIA-Secreted Phospholipase A(2) from Snake Venom. PLoS One, v. 9, n. 4, . (11/21341-5, 10/06345-1)
GIANNOTTI, KARINA CRISTINA; LEIGUEZ, ELBIO; MOREIRA, VANESSA; NASCIMENTO, NEIDE GALVAO; LOMONTE, BRUNO; MARIA GUTIERREZ, JOSE; DE MELO, ROBSON LOPES; TEIXEIRA, CATARINA. A Lys49 Phospholipase A(2), Isolated from Bothrops asper Snake Venom, Induces Lipid Droplet Formation in Macrophages Which Depends on Distinct Signaling Pathways and the C-Terminal Region. BIOMED RESEARCH INTERNATIONAL, . (11/21341-5, 07/03337-5, 10/06345-1)
LEIGUEZ, ELBIO; GIANNOTTI, KARMA CRISTINA; VIANA, MARIANA DO NASCIMENTO; MATSUBARA, MARCIO HIDEKI; FERNANDES, CRISTINA MARIA; GUTIERREZ, JOSE MARIA; LOMONTE, BRUNO; TEIXEIRA, CATARINA. A Snake Venom-Secreted Phospholipase A(2) Induces Foam Cell Formation Depending on the Activation of Factors Involved in Lipid Homeostasis. Mediators of Inflammation, . (11/21341-5, 15/24701-3, 14/18549-1, 13/22610-5, 10/08506-2, 10/06345-1)
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
LEIGUEZ JUNIOR, Elbio. Study of factors involved in lipid droplets formation induced by a phospholipase A2, isoleted from snake venom: synthesis and lipid metabolismo.. 2015. Doctoral Thesis - Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) São Paulo.

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