Activation of NFkappaB is essential but not sufficient to stimulate mitogenesis of vascular smooth muscle cells.
This study investigates the role of the transcription factor NFkappaB in thrombin- and thrombin receptor activating peptide (TRAP, SFLLRNPNDKYEPYF)-induced mitogenesis of cultured bovine coronary artery smooth muscle cells (SMC). Stimulation of resting cells by thrombin (10 nM) or TRAP (10-100 microM) resulted in a comparable time-dependent activation of NFkappaB as detected by Western blotting and electrophoretic mobility shift assay (EMSA) of nuclear extracts. The NFkappaB activation was antagonized by N-acetyl-L-cysteine (20 mM) and pentoxifylline (0.5 mM). Thrombin caused a 3-4-fold increase in [3H]thymidine incorporation within 24 h which was prevented by inhibitors of NFkappaB activation. In contrast, TRAP did not cause any mitogenic response. These results demonstrate that activation of NFkappaB is an essential but not a sufficient signal for SMC mitogenesis.
Bretschneider
E
E
Zentrum für Vaskuläre Biologie und Medizin Erfurt der Friedrich-Schiller-Universität Jena, Germany.
Wittpoth
M
M
Weber
A A
AA
Glusa
E
E
Schrör
K
K
D000111:Acetylcysteine / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001158:Arteries / Q000378:metabolism; D015153:Blotting, Western; D002417:Cattle; D002455:Cell Division; D002478:Cells, Cultured; D003331:Coronary Vessels; D008969:Molecular Sequence Data; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D010431:Pentoxifylline / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D010455:Peptides; D011480:Protease Inhibitors / Q000494:pharmacology; D013917:Thrombin / Q000037:antagonists & inhibitors / Q000494:pharmacology; D013936:Thymidine / Q000378:metabolism; D014665:Vasodilator Agents / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D016328:NF-kappa B; D010446:Peptide Fragments; D010455:Peptides; D011480:Protease Inhibitors; D014665:Vasodilator Agents; C076901:thrombin receptor-activating peptide (P508-530); C016977:amastatin; D013917:Thrombin; D010431:Pentoxifylline; D013936:Thymidine; D000111:Acetylcysteine