Signal transduction pathways involved in the platelet aggregation induced by a D-49 phospholipase A2 isolated from Bothrops jararacussu snake venom.
Bothropstoxin-II (Bthtx-II), an Asp-49 phospholipase A(2) (D-PLA(2)) isolated from Bothrops jararacussu snake venom is able to induce platelet aggregation in a concentration-dependent manner. This effect was not due to the release of ADP from platelets since the aggregation was not suppressed by ADP scavenger systems. PMSF and PPACK were unable to inhibit Bthtx-II-induced platelet aggregation. Thus, a thrombin-like proaggregating activity of Bthtx-II can be excluded as its mechanism of action. On the other hand, indomethacin at low concentrations inhibited more markedly the ATP-release reaction than the aggregation induced by Bthtx-II, indicating that generation of cyclooxigenase products is not the most important event for the platelet aggregation reaction. It was also found that staurosporine and genistein suppressed both platelet aggregation and ATP-release reactions, but not the platelet shape-change induced by Bthtx-II. Substances that either directly activates adenylyl cyclase enzyme (forskolin and PGE(1)) or cell-permeant increasing agents (dibutyril-cAMP) inhibited in a concentration-dependent fashion, the platelet aggregation effects induced by the protein. It is concluded that Bthtx-II induces platelet aggregation and secretion through multiple signal transduction pathways.
Fuly
André L
AL
Departamento de Bioquímica Médica, ICB/CCS, Universidade Federal do Rio de Janeiro, 21941-590 Brazil.
Soares
Andreimar M
AM
Marcussi
Silvana
S
Giglio
José R
JR
Guimarães
Jorge A
JA
D000818:Animals; D017837:Bothrops; D003435:Crotalid Venoms / Q000201:enzymology*; D004305:Dose-Response Relationship, Drug; D054501:Group II Phospholipases A2; D010741:Phospholipases A / Q000302:isolation & purification / Q000494:pharmacology*; D054467:Phospholipases A2; D010974:Platelet Aggregation / Q000187:drug effects*; D011817:Rabbits; D030162:Reptilian Proteins; D015398:Signal Transduction / Q000187:drug effects*
D003435:Crotalid Venoms; D030162:Reptilian Proteins; D010741:Phospholipases A; D054501:Group II Phospholipases A2; D054467:Phospholipases A2; C072031:bothropstoxin II