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

Autor(es)

Giannotti, Karina Cristina ; Leiguez, Elbio ; Moreira, Vanessa ; Nascimento, Neide Galvao ; Lomonte, Bruno ; Maria Gutierrez, Jose ; de Melo, Robson Lopes ; Teixeira, Catarina

• Tipo de documento: Artigo Científico
• Fonte: BIOMED RESEARCH INTERNATIONAL; v. 2013, p. 14-pg., 2013-01-01.

Resumo

MT-II, a Lys49PLA(2) homologue devoid of catalytic activity from B. asper venom, stimulates inflammatory events in macrophages. e investigated the ability of MT-II to induce formation of lipid droplets (LDs), key elements of inflammatory responses, in isolated macrophages and participation of protein kinases and intracellular PLA(2)s in this effect. Influence of MT-II on PLI 2 recruitment and expression was assessed, and the effects of some synthetic peptides on LD formation were further evaluated. At noncytotoxic concentrations, MT-II directly activated macrophages to form LDs.. is effect was reproduced by a synthetic peptide corresponding to the C-terminal sequence 115-129 of MT-II, evidencing the critical role of C-terminus for MT-II-induced effect. Moreover, MT-II induced expression and recruitment of PLIN2. Pharmacological interventions with specific inhibitors showed that PKC, PI3K, ERK1/2, and iPLA(2), but not P38(MAPK) or cPLA(2), signaling pathways are involved in LD formation induced by MT-II. This sPLA(2) homologue also induced synthesis of PGE(2) that colocalized to LDs. In conclusion, MT-II is able to induce formation of LDs committed to PGE(2) formation in a process dependent on C-terminal loop engagement and regulated by distinct protein kinases and iPLA(2). LDs may constitute an important inflammatory mechanism triggered by MT-II in macrophages. (AU)

• Processo FAPESP: 07/03337-5 - Efeito de duas fosfolipases A2, isoladas do veneno de serpente, sobre vias de ativação do NF-kapa b relacionadas à expressão de COX-2 e de PGE sintase m-1: envolvimento do receptor de manose de macrófagos nesses eventos
• Beneficiário: Vanessa Moreira
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 10/06345-1 - Estudo dos fatores envolvidos na formação de corpúsculos lipídicos, induzidos por uma Fosfolipase A2, isolada do veneno de serpente: síntese e metabolismo de lipídios
• Beneficiário: Elbio Leiguez Junior
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 11/21341-5 - Estudo de mecanismos envolvidos na formação de corpúsculos lipídicos induzidos por uma fosfolipase A2 isolada do veneno da serpente Bothrops asper em macrófagos isolados: participação de fatores da homeostasia lipídica
• Beneficiário: Catarina de Fatima Pereira Teixeira
• Modalidade de apoio: Auxílio à Pesquisa - Regular