CONTRIBUTION OF RAS/MEK/MAPK SIGNAL TRANSDUCTION PATHWAY TO
PLD ACTIVATION IN ANGIOTENSIN II-INDUCED VASCULAR SMOOTH MUSCLE
Ljuca1, Dž. Ljuca2
and S. Nuhbegović1
of Physiology, School of Medicine 1, Department of Gynecology
and Obstetrics 2, Clinical Center University of Tuzla, Bosnia
Introduction: AIntroduction: Activated
Ras/MEK/MAPK signal transduction pathway has been implicated in
vascular smooth musle cell (VSMC) proloferation induced by different
hormons such as Norepinephrine and Angiotensin II (ANG II). It
plays an important role in pathogenesis of different cardiovascular
diseases. It has been shown that Angiotensin II directly activates
phospholipase D (PLD) in VSMC.
Aim: to determine whether PLD activation is mediated by
activated Ras/MEK/MAPK signal transduction pathway in Angiotensin
II-induced VSMC proliferation.
Methods: PLD activity has been measured by PLD assay using
rabbit polyclonal antibodies against PLD, MAPK activity by Western
blotting analysis using antiphospho-MAPK antibody and VSMC proliferation
by 3H-thymidine incorporation. All assays have been determined
in VSMC treated by Angiotensin II in presence or absance of different
Ras, MEK, MAPK and PLD inhibitors.
Results: Angiotensin II treatment significantly induced
VSMC proliferation. PLD and Ras/MEK/MAPK activities have been
highly elevated in Angiotensin treated cells. However, when cells
have been treated by ANG II in presence of FPT III, a Ras inhibitor
and PD-98059, a MAK-inhibitor, PLD activity was decreased.
Conclusion: Activated Ras/MEK/MAPK signal transduction pathway
mediates PLD activation in Angiotensin II-induced VSMC proliferation.