Differential effects of forskolin and phobol 12-myristate-13-acetate on the c-fos and c-jun mRNA expression in rat C6 glioma cells.
The effects of forskolin (FSK) and phobol 12-myristate-13-acetate (PMA) on c-fos and c-jun mRNA expressions in rat C6 glioma cells were studied. Both FSK and PMA increased the c-fos mRNA level. The C-jun mRNA level was decreased by FSK, whereas it was increased by PMA. The elevated c-fos mRNA level, induced by FSK or PMA, was significantly inhibited by dexamethasone (DEX). In contrast, DEX did not affect the FSK- and PMA-induced response of the c-jun mRNA level. Cycloheximide (CHX) caused a superinduction of the FSK- or PMA-induced c-fos mRNA level. Furthermore, CHX also potentiated the PMA-induced c-jun mRNA level. However, CHX did not affect the FSK-induced down-regulation of the c-jun mRNA level. When C6 glioma cells were incubated with PMA and FSK, the PMA-induced c-jun mRNA level was inhibited by FSK, whereas FSK did not affect the PMA-induced c-fos mRNA level. Our results suggest that the activations of PKA and PKC pathways have different roles in the regulation of the c-jun mRNA expression in rat C6 glioma cells. PKA activation can inhibit induction of the c-jun mRNA expression by PMA. In addition, DEX appears to have a selective inhibitory action against c-fos, but not c-jun, -mRNA expression that is regulated by PKA and PKC. On-going protein synthesis inhibition is required for the superinduction of the c-fos expression that is induced by PMA, or FSK and the PMA-induced c-jun mRNA level.
Lee
J K
JK
Department of Pharmacology and Institute of Natural Medicine, College of Medicine, Hallym University, Chunchon, Korea.
Won
J S
JS
Choi
M R
MR
Kim
Y H
YH
Suh
H W
HW
D000818:Animals; D015152:Blotting, Northern; D005576:Colforsin / Q000494:pharmacology*; D003513:Cycloheximide / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D016762:Genes, fos; D016758:Genes, jun; D005938:Glucocorticoids / Q000494:pharmacology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000502:physiology; D013755:Tetradecanoylphorbol Acetate / Q000031:analogs & derivatives* / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D005938:Glucocorticoids; D011500:Protein Synthesis Inhibitors; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D005576:Colforsin; C016658:phorbolol myristate acetate; D003907:Dexamethasone; D003513:Cycloheximide; D013755:Tetradecanoylphorbol Acetate