artículo científico
A snake venom secreted phospholipase A2 induces foam cell formation depending on the activation of factors involved in lipid homeostasis
Fecha
2018-06Registro en:
0962-9351
1466-1861
10.1155/2018/2547918
Autor
Leiguez, Elbio
do Nascimento Viana, Mariana
Hideki Matsubara, Márcio
Fernandes, Cristina Maria
Giannotti, Karina Cristina
Gutiérrez, José María
Lomonte, Bruno
Teixeira, Catarina de Fátima
Institución
Resumen
MT-III, a snake venom GIIA sPLA2, which shares structural and functional features with mammalian GIIA sPLA2s, activates
macrophage defense functions including lipid droplet (LDs) formation, organelle involved in both lipid metabolism and
inflammatory processes. Macrophages (MΦs) 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 sPLA2 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-γ and PPAR-β/δ and increased the protein levels of both transcription factors and CD36
in macrophages. Pharmacological interventions evidenced that PPAR-γ, PPAR-β/δ, and CD36 as well as the endoplasmic
reticulum enzymes ACAT and DGAT are essential for LD formation. Moreover, PPAR-β/δ, but not PPAR-γ, is involved in
MT-III-induced PLIN2 protein expression, and both PPAR-β/δ and PPAR-γ 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.