A Snake Venom-Secreted Phospholipase A(2) Induces Foam Cell Formation Depending on the Activation of Factors Involved in Lipid Homeostasis

Author(s)

Leiguez, Elbio ^[1] ; Giannotti, Karma Cristina ^[1] ; Viana, Mariana do Nascimento ^[1] ; Matsubara, Marcio Hideki ^[1] ; Fernandes, Cristina Maria ^[1] ; Gutierrez, Jose Maria ^[2] ; Lomonte, Bruno ^[2] ; Teixeira, Catarina ^[1]

Affiliation

^[1] Butantan Inst, Pharmacol Lab, Sao Paulo, SP - Brazil

^[2] Univ Costa Rica, Clodomiro Picado Inst, San Jose 11501 - Costa Rica

• Document type: Journal article
• Source: Mediators of Inflammation; 2018.
• Web of Science Citations: 0

Abstract

MT-III, a snake venom GIIA sPLA(2), which shares structural and functional features with mammalian GIIA sPLA(2)s, activates macrophage defense functions including lipid droplet (LDs) formation, organelle involved in both lipid metabolism and inflammatory processes. Macrophages (M Phi s) loaded with LDs, termed foam cells, characterize early blood vessel fatty-streak lesions during atherosclerosis. However, the factors involved in foam cell formation induced by a GIIA sPLA(2) are still unknown. Here, we investigated the participation of lipid homeostasis-related factors in LD formation induced by MT-III in macrophages. We found that MT-III activated PPAR-gamma and PPAR-beta/delta and increased the protein levels of both transcription factors and CD36 in macrophages. Pharmacological interventions evidenced that PPAR-gamma, PPAR-beta/delta, and CD36 as well as the endoplasmic reticulum enzymes ACAT and DGAT are essential for LD formation. Moreover, PPAR-beta/delta, but not PPAR-gamma, is involved in MT-III-induced PLIN2 protein expression, and both PPAR-beta/delta and PPAR-gamma upregulated CD36 protein expression, which contributes to MT-III-induced COX-2 expression. Furthermore, production of 15-d-PGJ2, an activator of PPARs, induced by MT-III, was dependent on COX-1 being LDs an important platform for generation of this mediator. (AU)

• FAPESP's process: 11/21341-5 - Studies on the mechanisms involved in lipid body formation induced by a snake venom phospholipase A2 in isolated macrophages: participation of lipid homeosthasis factors
• Grantee: Catarina de Fatima Pereira Teixeira
• Support Opportunities: Regular Research Grants
• FAPESP's process: 15/24701-3 - Studies of effects of a snake venom phospholipase A2 on cells from the adipose tissue: Adipogenesis and inflammatory response
• Grantee: Elbio Leiguez Junior
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 14/18549-1 - 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
• Grantee: Catarina de Fatima Pereira Teixeira
• Support Opportunities: Regular Research Grants
• FAPESP's process: 13/22610-5 - 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.
• Grantee: Karina Cristina Giannotti
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 10/08506-2 - Study of mechanisms involved in prostacyclin biosynthesis induced by a Phospholipase A2, isolated from Crotalus durissus terrificus snake venom: repercussion on anti-inflammatory effects
• Grantee: Márcio Hideki Matsubara
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 10/06345-1 - Study of factors involved in lipid bodies formation induced by a Phospholipase A2, isolated from Bothrops asper snake venom: synthesis and metabolism of lipids
• Grantee: Elbio Leiguez Junior
• Support Opportunities: Scholarships in Brazil - Doctorate