Secretory phospholipases A(2) isolated from Bothrops asper and from Crotalus durissus terrificus snake venoms induce distinct mechanisms for biosynthesis of prostaglandins E-2 and D-2 and expression of cyclooxygenases

Autor(es)

Moreira, Vanessa ^[1] ; Gutierrez, Jose Maria ^[2] ; Soares, Andreimar Martins ^[3] ; Zamuner, Stella Regina ^[1] ; Purgatto, Eduardo ^[4] ; Pereira Teixeira, Catarina de Fatima ^[1]

Afiliação do(s) autor(es)

^[1] Inst Butantan, Farmacol Lab, Sao Paulo - Brazil

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

^[3] Univ Sao Paulo, Fac Ciencias Farmaceut, Dept Anal Clin Toxicol & Bromatol, BR-14049 Ribeirao Preto - Brazil

^[4] Univ Sao Paulo, Fac Ciencias Farmaceut, Dept Alimentos & Nutr Expt, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Toxicon; v. 52, n. 3, p. 428-439, SEP 1 2008.
• Citações Web of Science: 28

Resumo

The effects of myotoxin III (MT-III), a phospholipase A(2) (sPLA(2)) from Bothrops asper snake venom, and crotoxin B (CB), a neurotoxic and myotoxic sPLA2 from the venom of Crotalus durissus terrificus, on cyclooxygenases (COXs) expression and biosynthesis of prostaglandins (PGs) were evaluated, together with the mechanisms involved in these effects. Upon intraperitoneal injection in mice, both sPLA(2)s promoted the synthesis of PGD(2) and PGE(2), with a different time-course. MT-III, but not CB, induced COX-2 expression by peritoneal leukocytes without modification on COX-1 constitutive expression, whereas CB increased the constitutive activity of COX-1. MT-III increased the enzymatic activity of COX-1 and COX-2. Similar effects were observed when these sPLA(2)s were incubated with isolated macrophages, evidencing a direct effect on these inflammatory cells. Moreover, both toxins elicited the release of arachidonic acid from macrophages in vitro. inhibition of cPLA(2) by AACOCF(3), but not of iPLA(2) by PACOCF(3) or BEL, significantly reduced PGD2, PGE2 and arachidonic acid (AA) release promoted by MT-III. These inhibitors did not affect MT-III-induced COX-2 expression. In contrast, cPLA2 inhibition did not modify the effects of CB, whereas iPLA2 inhibition reduced PGD2 and AA production induced by CB. These findings imply that distinct regulatory mechanisms leading to PGs' synthesis are triggered by these snake venom sPLA(2)s. Such differences are likely to explain the dissimilar patterns of inflammatory reaction elicited by these sPLA(2)s in vivo. (C) 2008 Elsevier Ltd. All rights reserved. (AU)

• Processo FAPESP: 07/03336-9 - Estudo de efeitos de duas fosfolipases A2, isoladas do veneno de serpente, sobre vias de ativação do NF-kB relacionados à expressão de COX-2 e de PGE sintase M-1: envolvimento do receptor de manose
• Beneficiário: Catarina de Fatima Pereira Teixeira
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 02/13863-2 - Efeitos dos venenos de Bothrops asper e de Crotalus durissus terrificus, das miotoxinas MT-II e MT-III, crotoxina e crotapotina sobre a liberação de prostanóides e a expressão de ciclooxigenases: estudos in vivo e in vitro
• Beneficiário: Catarina de Fatima Pereira Teixeira
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 02/13458-0 - Estudo dos efeitos de toxinas com estrutura de fosfolipase a2 isoladas do veneno de bothrops asper e da crotoxina do veneno de crotalus durissus terrificus sobre a expressao de ciclooxigenases...
• Beneficiário: Vanessa Moreira
• Modalidade de apoio: Bolsas no Brasil - Doutorado