ROLE OF NF-KAPPAB IN PLATELETS: IMPAIRED ACTIVATION RESPONSES BY NF-KAPPAB INHIBITORS.

MALAVER, ELISA; ROMANIUK, MARÍA A.; DATRI, LINA P.; POZNER, ROBERTO G.; ETULAIN, JULIA; BENZADON, RICARDO; SCHATTNER, MIRTA

Aguas de Lindoia.

Congreso; XXXVIII Annual Meeting of the Brazilian Biochemistry and Molecular Biology Society.; 2009

Brazilian Biochemistry and Molecular Biology Society.

We have previously demonstrated that specific inhibition of NF-κB activation with Bay 11-7082 (Bay) impairs platelet function, suggesting a novel non-genomic role of this transcription factor on platelet activation. In the present study, the mechanisms involved in the action of Bay were further analyzed. Filopodia and lamellipodia formation associated to cytoskeleton reorganization are the first morphological changes observed on stimulated platelets. Both phenomena were significantly decreased in the presence of Bay (detected by actin polymerization, fluorescent microscopy). Platelet stimulation with classical agonists induced NF-κB activation (determined by binding of NF-κB to its DNA regulatory sequences by ELISA, n=3), which was prevented by treatment with Bay. Aggregation (measured by light transmission aggregometry), intraplatelet ATP release (luminescence), and TXB2 generation (ELISA) were not modified by incubation with Bay indicating that cyclo-oxigenase pathway is not affected. However, generation of TXB2 mediated by agonists that induce endogenous araquidonic acid synthesis, as well as cytosolic PLA2 activity (colorimetric assay) were inhibited 64±8% and 25±7% respectively in the presence of Bay (n=3, p