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We 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<jats:sub>2<\/jats:sub>s in this effect. Influence of MT-II on PLIN2 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. This effect was reproduced by a synthetic peptide corresponding to the C-terminal sequence 115\u2013129 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<jats:sub>2<\/jats:sub>, but not<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M2\"><mml:mrow><mml:msup><mml:mrow><mml:mtext>P38<\/mml:mtext><\/mml:mrow><mml:mrow><mml:mtext>MAPK<\/mml:mtext><\/mml:mrow><\/mml:msup><\/mml:mrow><\/mml:math>or cPLA<jats:sub>2<\/jats:sub>, signaling pathways are involved in LD formation induced by MT-II. This sPLA<jats:sub>2<\/jats:sub>homologue also induced synthesis of PGE<jats:sub>2<\/jats:sub>that colocalized to LDs. In conclusion, MT-II is able to induce formation of LDs committed to PGE<jats:sub>2<\/jats:sub>formation in a process dependent on C-terminal loop engagement and regulated by distinct protein kinases and iPLA<jats:sub>2<\/jats:sub>. LDs may constitute an important inflammatory mechanism triggered by MT-II in macrophages.<\/jats:p>","DOI":"10.1155\/2013\/807982","type":"journal-article","created":{"date-parts":[[2012,12,24]],"date-time":"2012-12-24T21:01:00Z","timestamp":1356382860000},"page":"1-14","source":"Crossref","is-referenced-by-count":6,"title":["A Lys49 Phospholipase<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M1\"><mml:mrow><mml:msub><mml:mtext>A<\/mml:mtext><mml:mtext>2<\/mml:mtext><\/mml:msub><\/mml:mrow><\/mml:math>, Isolated from<i>Bothrops asper<\/i>Snake Venom, Induces Lipid Droplet Formation in Macrophages Which Depends on Distinct Signaling Pathways and the C-Terminal Region"],"prefix":"10.1155","volume":"2013","author":[{"given":"Karina","family":"Cristina Giannotti","sequence":"first","affiliation":[{"name":"Laboratory of Pharmacology, Butantan Institute, Avenida Vital Brazil, 05503-900 S\u00e3o Paulo, SP, 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