A Lipidomic Perspective of the Action of Group IIA Secreted Phospholipase A(2)on Human Monocytes: Lipid Droplet Biogenesis and Activation of Cytosolic Phospholipase A(2)alpha

Autor(es)

Rodriguez, Juan P. ^{[1, 2]} ; Leiguez, Elbio ^{[1, 3]} ; Guijas, Carlos ^{[1, 4]} ; Lomonte, Bruno ^[5] ; Gutierrez, Jose M. ^[5] ; Teixeira, Catarina ^[3] ; Balboa, Maria A. ^{[1, 4]} ; Balsinde, Jesus ^{[1, 4]}

Afiliação do(s) autor(es)

^[1] Univ Valladolid, CSIC, Inst Biol & Genet Mol, Valladolid 47003 - Spain

^[2] Univ Nacl Nordeste, UNNE, Lab Invest Bioquim, CONICET, Inst Quim Basica & Aplicada Nordeste Arge, Consejo Nacl Invest Cient & Tecn, Fac Med LIBIM, RA-3400 Corrientes - Argentina

^[3] Inst Butantan, Lab Farmacol, BR-01000 Sao Paulo - Brazil

^[4] Ctr Invest Biomed Red Diabet & Enfermedades Metab, Madrid 28029 - Spain

^[5] Univ Costa Rica, Fac Microbiol, Inst Clodomiro Picado, San Jose 115012060 - Costa Rica

• Tipo de documento: Artigo Científico
• Fonte: BIOMOLECULES; v. 10, n. 6 JUN 2020.
• Citações Web of Science: 0

Resumo

Phospholipase A(2)s constitute a wide group of lipid-modifying enzymes which display a variety of functions in innate immune responses. In this work, we utilized mass spectrometry-based lipidomic approaches to investigate the action of Asp-49 Ca2+-dependent secreted phospholipase A(2)(sPLA(2)) (MT-III) and Lys-49 sPLA2 (MT-II), two group IIA phospholipase A(2)s isolated from the venom of the snakeBothrops asper, on human peripheral blood monocytes. MT-III is catalytically active, whereas MT-II lacks enzyme activity. A large decrease in the fatty acid content of membrane phospholipids was detected in MT III-treated monocytes. The significant diminution of the cellular content of phospholipid-bound arachidonic acid seemed to be mediated, in part, by the activation of the endogenous group IVA cytosolic phospholipase A(2)alpha. MT-III triggered the formation of triacylglycerol and cholesterol enriched in palmitic, stearic, and oleic acids, but not arachidonic acid, along with an increase in lipid droplet synthesis. Additionally, it was shown that the increased availability of arachidonic acid arising from phospholipid hydrolysis promoted abundant eicosanoid synthesis. The inactive form, MT-II, failed to produce any of the effects described above. These studies provide a complete lipidomic characterization of the monocyte response to snake venom group IIA phospholipase A(2), and reveal significant connections among lipid droplet biogenesis, cell signaling and biochemical pathways that contribute to initiating the inflammatory response. (AU)

• Processo FAPESP: 12/06730-8 - Estudo do papel da PLIN2 na resposta inflamatória induzida pela MT-III, uma Fosfolipase A2 isolada do veneno da serpente Bothrops asper: formação de corpúsculos lipídicos e liberação de mediadores inflamatórios
• Beneficiário: Elbio Leiguez Junior
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Doutorado