Regulation of nerve growth factor biosynthesis by beta-adrenergic receptor activation in astrocytoma cells: a potential role of c-Fos protein.
The chain of events that results in increased production of nerve growth factor (NGF) following beta-adrenergic receptor (BAR) stimulation has been investigated in the C6-2B rat astrocytoma cell line. Exposure of these cells to the BAR agonist isoproterenol elicits the following cascade of events: (i) increase of cAMP content; (ii) increase of c-Fos mRNA content; (iii) accumulation of c-Fos protein immunoreactivity in the nucleus; (iv) increase of NGF mRNA content. The increase in c-Fos mRNA and its translation product are early events (15 and 40 min, respectively) and precede the accumulation of NGF mRNA, which peaks at 3 hr. The increase in the two mRNAs appears interrelated because cycloheximide inhibits the accumulation of c-Fos protein and NGF mRNA elicited by isoproterenol. Moreover, the accumulation of nuclear c-Fos protein and NGF mRNA induced by BAR stimulation is reduced by 2-aminopurine, an inhibitor of c-Fos mRNA induction. These data suggest that, in C6-2B astrocytoma cells, the nuclear accumulation of c-Fos protein is required for the induction of NGF mRNA expression by BAR stimulation.
Mocchetti
I
I
Fidia-Georgetown Institute for the Neurosciences, Georgetown University, School of Medicine, Washington, DC 20007.
De Bernardi
M A
MA
Szekely
A M
AM
Alho
H
H
Brooker
G
G
Costa
E
E
D015075:2-Aminopurine / Q000494:pharmacology; D000818:Animals; D001254:Astrocytoma / Q000503:physiopathology*; D015152:Blotting, Northern; D000242:Cyclic AMP / Q000378:metabolism; D003513:Cycloheximide / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology; D009414:Nerve Growth Factors / Q000096:biosynthesis* / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology*; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D013997:Time Factors; D014407:Tumor Cells, Cultured
D009414:Nerve Growth Factors; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D011943:Receptors, Adrenergic, beta; D015075:2-Aminopurine; D003513:Cycloheximide; D000242:Cyclic AMP; D007545:Isoproterenol