Js. Lee et al., SYNCHRONIZATION OF CULTURED VASCULAR SMOOTH-MUSCLE CELLS FOLLOWING REVERSAL OF QUIESCENCE INDUCED BY TREATMENT WITH THE ANTIOXIDANT N-ACETYLCYSTEINE, Experimental cell research, 239(2), 1998, pp. 447-453
Smooth muscle cell (SMC) proliferation plays an important role in the
pathogenesis of vascular diseases such as atherosclerosis and postangi
oplasty restenosis. Recently we demonstrated the thiol antioxidant N-a
cetylcysteine (NAC) inhibits constitutive NF-kappa B/Rel activity and
growth of vascular SMCs. Here we show that treatment of human and bovi
ne aortic SMC with the thiol antioxidant NAC causes cells to exit the
cell cycle and remain quiescent as determined by a greatly reduced inc
orporation of [H-3]thymidine and G(0)/G(1) DNA content. Removal of NAC
from the culture medium stimulates SMCs to synchronously reenter the
cell cycle as judged by induction of cyclin D1 and B-myb gene expressi
on during mid and late G(1) phase, respectively, and induction of hist
one gene expression and [H-3]thymidine incorporation during S phase. T
he time course of cyclin D1, B-myb, and histone gene expression after
NAC removal was similar to that of serum-deprived cells induced to res
ume cell cycle progression by the addition of fetal bovine serum to th
e culture medium. Taken together, these results indicate that NAC trea
tment causes SMCs to enter a reversible G(0) quiescent, growth-arreste
d state. Thus, NAC provides an important new method for synchronizing
SMCs in culture. (C) 1998 Academic Press.