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Studies on the effects of a Phospholipase A2 isolated from Bothrops asper snake venom on smooth muscle vascular cells in culture. formation of lipid droplets and mechanisms involved in this effect

Grant number: 13/22610-5
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): March 01, 2014
Effective date (End): April 30, 2017
Field of knowledge:Biological Sciences - Pharmacology
Principal Investigator:Catarina de Fatima Pereira Teixeira
Grantee:Karina Cristina Giannotti
Home Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
Associated scholarship(s):16/14046-0 - Study on the effects of MT-III, a snake venom secreted Phospholipase A2 (sPLA2), on isolated rat and human aortic vascular smooth muscle cells: dedifferentiation into a phagocytic active macrophage-like phenotype, BE.EP.DR

Abstract

Bothrops snake venoms contain high concentrations of secreted Phospholipases A2 (sPLA2). These enzymes present high grade of homology with mammalian group IIA-PLA2, which levels are marked increased during inflammatory diseases such as aterosclerosis. MT-III, is a GII-A Asp49-sFLA2 isolated from Bothrops asper venom. Besides myotoxicity, this enzyme induces a pronounced inflammatory reaction both in vivo and in vitro models. In vitro, MT-III activates macrophages functions, including production of microbicidal agents, phagocytosis, release of arachidonic acid, lipid mediators and cytokines. Moreover, this sPLA2 is able to stimulate macrophages for formation of lipid bodies (LBs) and expression of perilipin 2 (PLIN2), an enzyme involved in lipid metabolism as well as on their accumulation into LBs. However, the effects of MT-III and of mammalian sPLA2s in smooth muscle vascular cells (SMVCs), wich also accumulate lipids into LBs and contribute to development of aterosclerosis and cardiovascular diseases are still unknown. Therefore, in this study the effects of MT-III on SMVCs will be investigated with focus on LB formation and the mechanisms involved. To this purpose, we will evaluate the following: i) formation of LBs, ii) cell distribution and gene and protein expression of PLIN2 and PLIN3, iii) expression of CD36 and SRA-1 receptors, iv) expression and activation of receptors PPAR-gama and PPAR-delata/beta, v) participation of the enzymes DGAT e ACAT, receptors CD36 and SRA1, PPAR-gama and PPAR-delta/beta in LBs formation, vi) release and cell distribution of prostaglandin E2, vii) release of TNF-alpha, IL-1, MCP-1 and fractalkine and viii) expression of ABCA1 and ABCG1. This study may contribute to the knowledge on the actions of sPLA2 during inflammatory processes and those associated to lipid unbalance. Moreover, this study is potentially relevant for discovery of new therapeutic targets in diseases associated to lipid unbalance. On the other hand, this investigation may contribute for a better understanding of the local reaction induced by Bothrops snake venoms.

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, 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, 2018. Web of Science Citations: 0.
GIANNOTTI, KARINA CRISTINA; LEIGUEZ, ELBIO; ZULIM DE CARVALHO, ANA EDUARDA; NASCIMENTO, NEIDE GALVAO; MATSUBARA, MARCIO HIDEKI; FORTES-DIAS, CONSUELO LATORRE; MOREIRA, VANESSA; TEIXEIRA, CATARINA. A snake venom group IIA PLA2 with immunomodulatory activity induces formation of lipid droplets containing 15-d-PGJ(2) in macrophages. SCIENTIFIC REPORTS, v. 7, JUN 22 2017. Web of Science Citations: 2.

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