Differential expressions of cell cycle regulatory proteins and ERK1/2 characterize the proliferative smooth muscle cell phenotype induced by allylamine

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Title: Differential expressions of cell cycle regulatory proteins and ERK1/2 characterize the proliferative smooth muscle cell phenotype induced by allylamine
Author: Jones, Sarah Anne Louise
Abstract: Chronic oxidative injury by allylamine induces proliferative vascular smooth muscle cell (vSMC ) phenotypes in the rat aorta similar to those seen in rodent and human atherosclerotic lesions . In this study , we evaluate the potential role of cyclin dependent kinase inhibitors , p21 and p27 , and extracellular regulated kinases (ERK1 /2 ) to mediate the proliferative advantage of oxidatively stressed (i .e . allylamine injured ) vSMC . Isolated rat aortic SMC from allylamine treated and control rats were cultured on different extracellular matrix (ECM ) proteins . Following mitogen restriction , cultures were stimulated with serum with or without inhibitors of NF -kB or MEK . Western blot analysis was performed to identify protein differences between treatment groups . Basal levels of p21 were 1 .6 fold higher in randomly cycling allylamine cells than control counterparts seeded on a plastic substrate , a difference lost when cells were seeded on collagen . p27 levels were comparable in both cell types irrespective of substrate . Basal levels of p21 and p27 were 1 .4 fold higher in G0 synchronized allylamine cells compared with G0 synchronized control cells seeded on a plastic substrate . Following cell cycle progression , differences in protein levels were not detected . Treatment with 100 nM pyrollidine dithiocarbamate (PDTC ) resulted in significant decreases in p21 and p27 in allylamine cells versus control cells following serum stimulation for 9 hours . This decrease was even greater for p21 in allylamine cells when grown on collagen relative to control cells . Alterations in peak and temporal activation of ERK1 /2 were observed in allylamine cells seeded on a plastic substrate as compared to control cells , following serum stimulation . Seeding on collagen decreased the enhanced peak phosphorylation of ERK1 /2 and increased the sustained activity in allylamine cells compared with control counterparts . Inhibition of ERK1 /2 activity resulted in reduced p21 expression in both cells types , but the response was markedly enhanced in allylamine cells , and preferentially observed on a restrictive collagen substrate . We conclude that induction of proliferative (i .e . atherogenic ) phenotypes following repeated cycles of oxidative injury involves ERK1 /2 activity and modulation of the cyclin dependent kinase inhibitors , p21 and p27 , in a matrix -dependent manner .
URI: http : / /hdl .handle .net /1969 .1 /124
Date: 2004-09-30

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Differential expressions of cell cycle regulatory proteins and ERK1/2 characterize the proliferative smooth muscle cell phenotype induced by allylamine. Available electronically from http : / /hdl .handle .net /1969 .1 /124 .

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