Rj. Hendrickson et al., Ethanol inhibits mitogen activated protein kinase activity and growth of vascular smooth muscle cells in vitro, EUR J PHARM, 362(2-3), 1998, pp. 251-259
The aim of this study was to determine the effect of ethanol on vascular sm
ooth muscle cell proliferation and mitogen activated protein kinase (MAPK)
signaling. Rat aortic smooth muscle cell growth in vitro was determined by
measuring cell counts and [H-3]thymidine incorporation. MAPK signaling was
determined by assessing MEK (also referred to as MAPK kinase) activity by m
easuring phosphorylated extracellular signal-regulated kinase ((pp)44ERK-1
and (pp)42ERK- 2) expression, and ERK activity by measuring ERK-2-dependent
phosphorylation of myelin basic protein (MBP). In quiesced smooth muscle c
ells, ethanol treatment (24 h) inhibited serum-stimulated mitogenesis in a
dose-dependent manner, (IC50 = 60 mM), in the absence of any effect on smoo
th muscle cell viability. In addition, ethanol treatment caused a significa
nt shift to the right in the smooth muscle cell growth curve, extending the
population doubling time from similar to 48 h (control) to similar to 70 h
(ethanol). Acute (15 min) ethanol treatment reduced serum-stimulated (pp)4
4ERK - 1 and (pp)42ERK - 2 expression in a dose dependent fashion; 24.5 +/-
1.546 and 77.6 +/- 3.2% inhibition for 20 mM and 160 mM ethanol, respectiv
ely. Furthermore, there was a significant dose-dependent decrease in ERK2 a
ctivity in ethanol treated smooth muscle cells as compared to control smoot
h muscle cells. These data demonstrate an inhibitory effect of ethanol on s
mooth muscle cell proliferation and MAPK signalling in vitro. It is temptin
g to speculate that these actions of ethanol may contribute to its cardiova
scular effects in vivo. (C) 1998 Elsevier Science B.V. All rights reserved.