NF-kappaB NON GENOMIC SIGNAL IN PLATELET.

MALAVER, ELISA; D’ATRI, LINA P.; POZNER, ROBERTO G.; NEGROTTO, SOLEDAD; PACIENZA, NATALIA; BENZADON, R; LAZZARI, MARIA A.; SCHATTNER, MIRTA

Estambul, Turquia.

Congreso; 77th Congress of the European Atherosclerosis Society.; 2008

European Atherosclerosis Society.

The NF-kB/I-kB complex plays a critical role in regulating the expression of genes involved in differentiation, proliferation, inflammation, oncogenesis and apoptosis. It has been previously reported that platelets express NF-êB and that stimulation with thrombin (TR) induces I-kB degradation. However, the effects of NF-êB activation on platelet physiology are still unknown. We evaluated the role of NF-êB in platelet activation. Treatment of human platelets with the specific NF-êB inhibitor, Bay 11-7082 (Bay, 100 ìM) inhibited ADP, collagen and epinephrine induced aggregation (79±8, 70±8, 67±6% of inhibition, respectively; n=5, p<0.001). TR induced aggregation in washed platelets treated with Bay decreased 62±11% compared to control samples (n=8, p<0.001). Platelets ATP release (measured in a Chrono-Log Lumi aggregometer) stimulated by ADP was significantly diminished in the presence of Bay (2.84 ±1 vs 0.5±0.2 ìM, p<0.05, n=3). Exposure of fibrinogen binding sites (determined by PAC-1 binding) induced by TR was inhibited by Bay (C: 3±1, TR: 47±10, TR+Bay: 22±5 *% of PAC-1 positive cells, n=3, *p<0,05 vs TR). Western blot assays showed that stimulation of platelets with TR and ADP induced I-êB degradation and this effect was prevented by Bay. In order to analyze the role of NF-êB in platelet activation in vivo, mice were inoculated with Bay (10 mg/kg). After a 24 h treatment, platelet aggregation induced by ADP was decreased 57±3% compared to untreated mice (n=7, p<0.05). These findings suggest that NF-êB/Iê-B complex would be involved in platelet activation and reveal a novel non-genomic action of this transcription factor.