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Master's Dissertation
DOI
10.11606/D.87.2010.tde-18062010-130343
Document
Author
Full name
Sergio Augusto de Lima
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2010
Supervisor
Committee
Teixeira, Catarina de Fatima Pereira (President)
Gonçalves, Luis Roberto de Camargo
Silva, Ana Maria Moura da
Title in Portuguese
Estudo dos efeitos das serinoproteinases PA-BJ e Giroxinas isoladas de venenos de serpentes em cultura de células endoteliais
Keywords in Portuguese
Células endoteliais
Ciclooxigenase
Giroxina
PA-BJ
Prostaciclina
Serinoproteinase
Abstract in Portuguese
Neste estudo foram avaliados os efeitos das serinoproteinases PA-BJ e giroxina, isoladas dos venenos das serpentes Bothrops jararaca e Crotalus durissus terríficus, respectivamente, sobre células endoteliais (CEs) em cultura. Os resultados obtidos demonstraram que essas toxinas, nas concentrações utilizadas, não afetaram a viabilidade e a integridade das CEs. Por outro lado, induziram a liberação de PGI2, que foi significativamente reduzida por inibidores não seletivos e seletivos das ciclooxigenases -1 e -2 (COX-1 e -2), mas não afetaram a expressão protéica constitutiva das mesmas. Adicionalmente, foi demonstrado que o antagonista de receptores PAR-1, o SCH 79797, não alterou a liberação de PGI2, induzida pelas toxinas. Em conclusão, essas toxinas, em concentrações não citotóxicas, induziram a liberação de PGI2 a partir de CEs, de modo dependente da ativação das COX-1 e -2. Por outro lado, o receptor PAR-1 não parece ser importante para este efeito, nessas células.
Title in English
Studies on the effects of the serine proteinases PA-BJ and gyroxin, isolated from snake venoms, on endothelial cells in culture
Keywords in English
Cyclooxygenases
Endothelial cells
Gyroxin
PA-BJ
Prostacyclin
Serine proteinase
Abstract in English
In this study, the effects of PA-BJ and gyroxin, isolated from Bothrops jararaca and Crotalus durissus terrificus snake venoms, respectively, on endothelial cells in culture were investigated. Results showed that neither PA-BJ nor gyroxin affected the integrity of monolayers nor modified ECs viability in the periods of incubation tested. In contrast, these serine proteinases increased the release of prostacyclin from ECs. This effect was inhibited by both non-selective and selective COX-1 and COX-2 inhibitors, but these toxins did not affect the protein expression of COX-1 and -2. Inhibition of the catalytic activity of PA-BJ and gyroxin or pre-incubation of ECs with PAR-1 antagonist did not abrogate the ability of these toxins to induce PGI2 release. These findings demonstrate that these serine proteinases are able to stimulate production of prostacyclin by ECs by a mechanism dependent on stimulation of COX-1 and COX-2 enzyme activity. Moreover, neither enzyme activity of both serine proteinases nor the receptor PAR-1 contribute for this effect on endothelium.
 
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Publishing Date
2010-09-16
 
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