Modulation of cholinergic locus expression by glucocorticoids and retinoic acid is cell-type specific.
Modulation of mRNA expression of choline acetyltransferase (ChAT) and the vesicular acetylcholine transporter (VAChT) by the glucocorticoid dexamethasone and by retinoic acid was examined in two neuronal cell lines: basal forebrain-derived SN56 and pheochromocytoma PC12. Dexamethasone up-regulated ChAT and VAChT in SN56 cells, while it had inhibitory effects on these genes in PC12 cells. Retinoic acid stimulated the cholinergic markers in both cell types, but in SN56 cells its effect was partially additive with that of dexamethasone, whereas it was much smaller and abrogated by dexamethasone in PC12 cells. Acetylcholine content correlated with these mRNA changes. The presence of a glucocorticoid response element consensus sequence in the VAChT/ChAT gene locus suggests direct transcriptional regulation by glucocorticoids.
Berse
B
B
Department of Pathology, Boston University School of Medicine, MA 02118, USA.
Blusztajn
J K
JK
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D015152:Blotting, Northern; D002352:Carrier Proteins / Q000235:genetics*; D002460:Cell Line; D002795:Choline O-Acetyltransferase / Q000235:genetics*; D003907:Dexamethasone / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D005938:Glucocorticoids / Q000494:pharmacology; D026901:Membrane Transport Proteins; D051379:Mice; D016716:PC12 Cells; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D014212:Tretinoin / Q000494:pharmacology*; D050494:Vesicular Acetylcholine Transport Proteins; D033921:Vesicular Transport Proteins
D002352:Carrier Proteins; D005938:Glucocorticoids; D026901:Membrane Transport Proteins; D012333:RNA, Messenger; C493460:Slc18a3 protein, mouse; C493461:Slc18a3 protein, rat; D050494:Vesicular Acetylcholine Transport Proteins; D033921:Vesicular Transport Proteins; D014212:Tretinoin; D003907:Dexamethasone; D002795:Choline O-Acetyltransferase; D000109:Acetylcholine