B-50/GAP-43 mRNA expression in cultured primary Schwann cells is regulated by cyclic AMP.
Following peripheral nerve crush or transection, B-50 mRNA expression increased dramatically in the distal nerve stump. This increase has been fully attributed to an up-regulation of B-50 synthesis in reactive Schwann cells. Here we describe that B-50 mRNA expression in primary Schwann cell cultures is strongly down-regulated by cyclic AMP. Treatment of neonatal Schwann cell cultures with as low as 20 nM forskolin decreased B-50 mRNA expression. We show that B-50 promoter P2, but not P1, is active in Schwann cells and that the activity of P2 is inhibited 2.5 fold by forskolin. P2 does not contain a consensus sequence of a known cyclic AMP responsive element suggesting that the effect of forskolin is indirect.
Plantinga
L C
LC
Department of Medical Pharmacology, Rudolf Magnus Institute for Neurosciences, Utrecht University.
Schrama
L H
LH
Eggen
B J
BJ
Gispen
W H
WH
Verhaagen
J
J
Lemke
G
G
D000818:Animals; D000831:Animals, Newborn; D001358:Avian Sarcoma Viruses / Q000235:genetics; D002478:Cells, Cultured; D003001:Cloning, Molecular; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D019922:GAP-43 Protein; D008156:Luciferases / Q000235:genetics; D008562:Membrane Glycoproteins / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010750:Phosphoproteins / Q000235:genetics; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012583:Schwann Cells / Q000378:metabolism*; D014162:Transfection
D019922:GAP-43 Protein; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D010750:Phosphoproteins; D012333:RNA, Messenger; D005576:Colforsin; D000242:Cyclic AMP; D008156:Luciferases