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

Author(s)

Giannotti, Karina Cristina ^[1] ; Leiguez, Elbio ^[1] ; Moreira, Vanessa ^[1] ; Nascimento, Neide Galvao ^[1] ; Lomonte, Bruno ^[2] ; Maria Gutierrez, Jose ^[2] ; de Melo, Robson Lopes ^[3] ; Teixeira, Catarina ^[1]

Affiliation

^[1] Butantan Inst, Pharmacol Lab, BR-05503900 Sao Paulo - Brazil

^[2] Univ Costa Rica, Sch Microbiol, Inst Clodomiro Picado, San Jose 2060 - Costa Rica

^[3] Butantan Inst, CAT, BR-05503900 Sao Paulo - Brazil

• Document type: Journal article
• Source: BIOMED RESEARCH INTERNATIONAL; 2013.
• Web of Science Citations: 11

Abstract

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)

• 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 type: Scholarships in Brazil - Doctorate
• 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 type: Regular Research Grants
• FAPESP's process: 07/03337-5 - Effects of two phospholipases A2, isolated from snake venom on NF-kappaB activation pathways related to COX-2 and mPGE synthase-1 expression: involvement of macrophage mannose receptors
• Grantee: Vanessa Moreira
• Support type: Scholarships in Brazil - Post-Doctorate