Astrocytes regulate GFAP mRNA levels by cyclic AMP and protein kinase C-dependent mechanisms.
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-methylxanthine 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.
Shafit-Zagardo
B
B
Department of Pathology, Albert Einstein College of Medicine, Bronx, New York 10461.
Kume-Iwaki
A
A
Goldman
J E
JE
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D003994:Bucladesine / Q000494:pharmacology; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism*; D006801:Humans; D011493:Protein Kinase C / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D005904:Glial Fibrillary Acidic Protein; D012333:RNA, Messenger; D005576:Colforsin; D003994:Bucladesine; D000242:Cyclic AMP; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D015056:1-Methyl-3-isobutylxanthine