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| Author(s): |
Márcio Hideki Matsubara
Total Authors: 1
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| Document type: | Doctoral Thesis |
| Press: | São Paulo. |
| Institution: | Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) |
| Defense date: | 2015-06-18 |
| Examining board members: |
Catarina de Fatima Pereira Teixeira;
Sandra Helena Poliselli Farsky;
Richardt Gama Landgraf;
Anderson de Sá Nunes;
Heraldo Possolo de Souza
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| Advisor: | Catarina de Fatima Pereira Teixeira |
| Abstract | |
In this study the effect of CB, a phospholipase A2 (PLA2) isolated from Crotalus durissus terrificus snake venom, in cultured endothelial cells was investigated, with focus on: i) biosynthesis of prostacyclin (PGI2) and related mechanisms, and ii) inhibitory mechanisms on expression of ICAM-1, VCAM-1 and PECAM-1 adhesion molecules. Results showed that COX-1, PGI2 synthase (PGIS), cPLA2, ERK1/2 and MEK1/2, but not COX-2, NF-kB, p38, JNK, iPLA2, IP receptor, cyclase adenylate nor PKA, are involved CB-induced PGI2 biosynthesis. In addition, CB up-regulated PGIS, but not COX-1 nor COX-2 protein levels. Moreover, CB was able to inhibit LPS-induced ICAM-1 and VCAM-1, but not PECAM-1 protein expression. PPAR-α and -β/δ, IP receptor, cyclase adenylate, PKA and PGI2, but not PPAR-γ, are essential for CB-induced inhibition of ICAM-1. Furthermore, CB inhibited LPS-induced gene expression of ICAM-1, VCAM-1, TNF-α and IL-6. Inhibition of these cytokines by CB may be related to down regulation of both VCAM-1 and ICAM-1 seen in endothelial cells incubated with this venom PLA2. (AU) | |
| FAPESP's process: | 10/08506-2 - Study of mechanisms involved in prostacyclin biosynthesis induced by a Phospholipase A2, isolated from Crotalus durissus terrificus snake venom: repercussion on anti-inflammatory effects |
| Grantee: | Márcio Hideki Matsubara |
| Support Opportunities: | Scholarships in Brazil - Doctorate |