TY - JOUR
T1 - Astrocytes regulate GFAP mRNA levels by cyclic AMP and protein kinase C‐dependent mechanisms
AU - Shafit‐Zagardo, Bridget
AU - Kume‐Iwaki, Akiko
AU - Goldman, James E.
PY - 1988
Y1 - 1988
N2 - Glial fibrillary acidic protein (GFAP) mRNA and protein levels in rat astrocyte cultures and in the human astrocytoma line U‐373MG were examined in order to determine the effects of agents that regulate cAMP‐dependent kinase and protein kinase C. Treatment of cells with dibutyryl cAMP or forskolin and 3‐isobutyl‐1‐methylxan‐thine increased steady‐state GFAP mRNA levels. Short‐term treatment of cells with phorbol‐12‐myristate‐13‐acetate (PMA) increased GFAP mRNA levels, but prolonged treatment of cells with PMA or 1‐oleoyl‐2‐acetyl‐rac‐glycerol produced a dramatic decrease in GFAP mRNA; 4‐beta‐phorbol had no effect. Thus, both cAMP‐dependent kinase and protein kinase C may exert regulatory roles in determining GFAP mRNA levels. Nuclear run‐off studies showed no change in GFAP mRNA synthesis after cAMP or PMA treatment, suggesting post‐transcriptional mechanisms. Western blot analysis revealed that the effect of PMA on U‐373MG cells shows specificity in that GFA protein levels decline, while those of other major cytoskeletal proteins were unaltered.
AB - Glial fibrillary acidic protein (GFAP) mRNA and protein levels in rat astrocyte cultures and in the human astrocytoma line U‐373MG were examined in order to determine the effects of agents that regulate cAMP‐dependent kinase and protein kinase C. Treatment of cells with dibutyryl cAMP or forskolin and 3‐isobutyl‐1‐methylxan‐thine increased steady‐state GFAP mRNA levels. Short‐term treatment of cells with phorbol‐12‐myristate‐13‐acetate (PMA) increased GFAP mRNA levels, but prolonged treatment of cells with PMA or 1‐oleoyl‐2‐acetyl‐rac‐glycerol produced a dramatic decrease in GFAP mRNA; 4‐beta‐phorbol had no effect. Thus, both cAMP‐dependent kinase and protein kinase C may exert regulatory roles in determining GFAP mRNA levels. Nuclear run‐off studies showed no change in GFAP mRNA synthesis after cAMP or PMA treatment, suggesting post‐transcriptional mechanisms. Western blot analysis revealed that the effect of PMA on U‐373MG cells shows specificity in that GFA protein levels decline, while those of other major cytoskeletal proteins were unaltered.
KW - Central nervous system
KW - Glia
KW - Intermediate filaments
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U2 - 10.1002/glia.440010507
DO - 10.1002/glia.440010507
M3 - Article
C2 - 2465997
AN - SCOPUS:0024221264
VL - 1
SP - 346
EP - 354
JO - GLIA
JF - GLIA
SN - 0894-1491
IS - 5
ER -