Na. Jensen et al., CYCLIC-AMP HAS A DIFFERENTIATIVE EFFECT ON AN IMMORTALIZED OLIGODENDROCYTE CELL-LINE, Journal of neuroscience research, 35(3), 1993, pp. 288-296
We investigated the effects of increasing the concentration of intrace
llular cyclic adenosine monophosphate (cAMP) on genes associated with
oligodendrocyte differentiation in an immortalized glial cell line, 6E
12, derived from the spinal cord of an MBP-SV40 large T-antigen transg
enic mouse. Raising intracellular levels of cAMP induced expression of
oligodendrocyte differentiation antigens recognized by 04 and anti-ga
lactocerebroside antibodies, up-regulated expression of the proteolipi
d protein (PLP) gene, and down-regulated glial fibrillary acidic prote
in (GFAP) expression. There was no treatment effect on myelin-associat
ed glycoprotein (MAG) expression. These phenotypic changes are consist
ent with oligodendrocyte differentiation. Treatment of 6E12 cells with
dibutyryl cyclic AMP (DBC) down-regulated myelin basic protein (MBP)
gene expression, perhaps, because it also up-regulated expression of a
putative MBP repressor SCIP/Tst-1. Moreover, the 6E12 cells expressed
high levels of MBP mRNA but no MBP translation products were detected
in the presence or absence of DBC. This immortalized glial cell line
is proposed as a CNS model for cAMP-modulated myelin gene expression a
nd for post-transcriptional regulation of MBP.