Characterization of the effects of a snake venom Phospholipase A2 (MT-III) on smooth muscle vascular cells in culture: formation of foam cells and mechanisms involved in this effect

• Grant number: 14/18549-1
• Support Opportunities: Regular Research Grants
• Start date: February 01, 2015
• End date: January 31, 2017
• Field of knowledge: Biological Sciences - Pharmacology - Toxicology
• Principal Investigator: Catarina de Fatima Pereira Teixeira
• Grantee: Catarina de Fatima Pereira Teixeira
• Host Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

Secreted phospholipases A2 (sPLA2s) are major components of Bothrops snake venoms. These enzymes present high grade of homology with mammalian GIIA-PLA2s, which are markedly increased during inflammatory diseases such as atherosclerosis. Therefore, these snake enzymes constitute valuable tools for studies on the effects of mammalian inflammatory sPLA2s. MT-III, a GII-A Asp49-sFLA2 isolated from Bothrops asper venom, displays a pronounced inflammatory activity in both in vivo and in vitro experimental models. We have recently shown that MT-III induces formation of foam macrophages, characterized by increased amounts of lipid bodies (LBs) and expression of perilipin 2 (PLIN2), a protein involved in formation of LBs. However, the effects of MT-III and mammalian sPLA2s in smooth muscle vascular cells (SMVCs) are still unknown. SMVCs accumulate lipids into LBs upon inflammatory stimuli and are relevant cells in inflammatory diseases related to lipid unbalance, including atherosclerosis. In this study the effects of MT-III on SMVCs will be investigated with focus on LB formation and the mechanisms involved, evaluating: i) formation of LBs; ii) importance of MT-III enzyme activity and cell phenotype (synthetic and contractile) to LBs formation; iii) distribution and protein expression of PLIN2 and PLIN3; iv) expression and participation of CD36 and SRA-1 receptors in LBs formation; v) expression, activation and participation of receptors PPAR-gama and PPAR-delta/beta in LBs formation; vi) participation of the enzymes DGAT e ACAT in LBs formation; vii) expression of COX-1 and -2, release of PGE2 and intracellular distribution of these elements with regard LBs localization; viii) release of TNF-alpha, IL-1, IL-6, MCP-1 and fractalkine; ix) expression of ABCA1 and ABCG1 proteins and x) internalization of MT-III into CMLVs. This study will amplify the knowledge on the actions of sPLA2 during inflammatory processes, mainly those associated to lipid unbalance. Moreover, this study is potentially relevant for discovery of new therapeutic targets in diseases associated to lipid unbalance. In addition, this study will contribute to understand the inflammatory reaction induced by Bothrops snake venoms. (AU)

Scientific publications

(5)

(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. (11/21341-5, 15/24701-3, 14/18549-1, 13/22610-5, 10/08506-2, 10/06345-1)

ZULIM DE CARVALHO, ANA EDUARDA; GIANNOTTI, KARINA; LEIGUEZ JUNIOR, ELBIO; MATSUBARA, MARCIO; DOS SANTOS, MARIA CRISTINA; FORTES-DIAS, CONSUELO LATORRE; TEIXEIRA, CATARINA. Crotalus durissus ruruima Snake Venom and a Phospholipase A(2) Isolated from This Venom Elicit Macrophages to Form Lipid Droplets and Synthesize Inflammatory Lipid Mediators. JOURNAL OF IMMUNOLOGY RESEARCH, v. 2019, NOV 4 2019. (15/24701-3, 14/18549-1, 18/05637-0, 15/50040-4)

CASAIS-E-SILVA, LUCIANA LYRA; TEIXEIRA, CATARINA. Neurogenic mediators contribute to local edema induced by Micrurus lemniscatus venom. PLoS Neglected Tropical Diseases, v. 11, n. 11, NOV 2017. (14/18549-1)

GIANNOTTI, KARINA CRISTINA; WEINERT, SOENKE; VIANA, MARIANA NASCIMENTO; LEIGUEZ, ELBIO; ARAUJO, THAIS L. S.; LAURINDO, FRANCISCO R. M.; LOMONTE, BRUNO; BRAUN-DULLAEUS, RUEDIGER; TEIXEIRA, CATARINA. A Secreted Phospholipase A(2) Induces Formation of Smooth Muscle Foam Cells Which Transdifferentiate to Macrophage-Like State. Molecules, v. 24, n. 18, SEP 2019. (13/22610-5, 15/24701-3, 16/14046-0, 14/18549-1)

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, v. 2018, p. 13-pg., 2018-01-01. (10/06345-1, 11/21341-5, 15/24701-3, 14/18549-1, 10/08506-2, 13/22610-5)