KINASE/AKT/PKB SIGNAL TRANSDUCTION PATHWAY MEDIATES NOREPINEPHRINE-INDUCED
VASCULAR SMOOTH MUSCLE CELL PROLIFERATION
F. Ljuca1, Dž. Ljuca2
and S. Nuhbegović1
of Physiology, School of Medicine, Department of Gynecology
and Obstetrics, Clinical Center University of Tuzla, Bosnia
Introduction: Norepinephrine (NE) by binding
primarily a1 adrenergic receptors promotes vascular smooth muscle
cell (VSMC) proliferation. Activated PI-3 kinase/AKT/PKB signal
transduction pathway has been implicated in cell growth and VSMC
proliferation. Aim: To determine whether NE activates PI-3 kinase/AKT/PKB
signal transduction pathway in rabbit VSMC and by which mechanism.
Methods: PI-3 kinase activity has been
measured by PI-3 kinase assay; MAPK, AKT/PKB activities by Western
blotting analysis using antiphospho-MAPK and antiphospho-AKT/PKB
antibodies and VSMC proliferation by 3H-thymidine incorporation.
All assays have been determined in VSMC treated by NE in presence
or absance of different Ras, MEK, MAPK and PI-3 kinase inhibitors.
Results: NE treatment significantly induced VSMC proliferation.
PI-3 kinase, AKT/PKB and Ras/MEK/MAPK activities have been highly
elevated in NE treated cells. However, when cells have been treated
by NE in presence of FPT III, a Ras inhibitor, PI-3 kinase andAKT/PKB
activities were decreased.
Conclusion: NE induces VSMC proliferation
by activation Ras/MEK/MAPK signal transduction pathway that mediates
PI-3 kinase/AKT/PKB activation.