ADRENERGIC-DIFFERENTIATION POTENTIAL IN PC12 CELLS - INFLUENCE OF SODIUM-BUTYRATE AND DEXAMETHASONE

The ability of sodium butyrate and dexamethasone to promote adrenergic differentiation in PC12 cells was examined using the gene encoding th e epinephrine biosynthetic enzyme, phenylethanolamine N-methyltransfer ase (PNMT1), as a marker. Sodium butyrate and dexamethasone independen tly stimulated expression of PNMT mRNA in PC12 cells, and the combined action of these drugs led to synergistic activation of the PNMT gene. Despite the induction of the PNMT gene, epinephrine is not produced i n these cells, in part due to the absence of a corresponding induction in PNMT enzymatic activity. Another contributing factor appears to be a reduction in the precursor catecholamines, norepinephrine and dopam ine, in the presence of sodium butyrate. Thus, while sodium butyrate a nd dexamethasone can induce PNMT gene expression, treatment of PC12 ce lls with these drugs appears insufficient for full acquisition of the adrenergic phenotype. (C) 1997 Elsevier Science B.V. All rights reserv ed.