ACTIVATION OF NF-KAPPA-B IS ESSENTIAL BUT NOT SUFFICIENT TO STIMULATEMITOGENESIS OF VASCULAR SMOOTH-MUSCLE CELLS

This study investigates the role of the transcription factor NF kappa B in thrombin- and thrombin receptor activating peptide (TRAP, SFLLRNP NDKYEPYF)-induced mitogenesis of cultured bovine coronary artery smoot h muscle cells (SMC). Stimulation of resting cells by thrombin (10 nM) or TRAP (10-100 mu M) resulted in a comparable time-dependent activat ion of NF kappa B as detected by Western blotting and electrophoretic mobility shift assay (EMSA) of nuclear extracts. The NF kappa B activa tion was antagonized by N-acetyl-L-cysteine (20 mM) and pentoxifylline (0.5 mM). Thrombin caused a 3-4-fold increase in [H-3]thymidine incor poration within 24 h which was prevented by inhibitors of NF kappa B a ctivation. In contrast, TRAP did not cause any mitogenic response. The se results demonstrate that activation of NF kappa B is an essential b ut not a sufficient signal for SMC mitogenesis. (C) 1997 Academic Pres s.