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 the epinephrine biosynthetic enzyme, phenylethanolamine N-methyltransferase (PNMT), as a marker. Sodium butyrate and dexamethasone independently 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 in 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 dopamine, in the presence of sodium butyrate. Thus, while sodium butyrate and dexamethasone can induce PNMT gene expression, treatment of PC12 cells with these drugs appears insufficient for full acquisition of the adrenergic phenotype.