title: Regulation of proenkephalin expression in C6 rat glioma cells.
abstract: The expression of proenkephalin (PENK) mRNA in C6 rat glioma cells was stimulated by norepinephrine (a beta-adrenergic agonist) and markedly enhanced by the addition of dexamethasone (a glucocorticoid agonist) to the culture medium, although dexamethasone alone exhibited no significant increase in PENK mRNA. Furthermore, no induction of glucocorticoid-response-element (GRE)-binding proteins was detectable. In contrast, the stimulation of PENK mRNA expression was not observed with a protein kinase C activator, 12-tetradecanoylphorbol-13-acetate (TPA), which stimulated the expression of c-fos and c-jun mRNA and their proto-oncoproteins (c-Fos and c-Jun). In addition, an AP-1 activity was induced by TPA and an induction of a kappaB-like binding activity was found with TPA plus cycloheximide-treated cells. Together, they suggest that activation of PENK gene in C6 cells is probably mediated mainly through the, beta-adrenergic agonist-elicited cyclic AMP signal pathway, and induction of AP-1 and kappaB-like binding activities appear not to participate in gene activation. Interestingly, the Western blot data showed no increase in intracellular levels of proenkephalin between control and treated cells. However, a marked increase in immunoreactivities for proenkephalin and its derivative, [Met(5)]-enkephalin was detected in medium and a lesser elevation in cells from modulator-treated cell culture through the time course. These results indicated that there was an association between an increase in PENK mRNA expression and an elevation of proenkephalins, and subsequently, the synthesized proenkephalins were released into the medium.
authors.affiliation: Neuropharmacology Section, Laboratory of Molecular and Integrative Neuroscience, NIEHS/NIH, Research Triangle Park, North Carolina 27709, USA; Lineberger Comprehensive Cancer Research Center, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
authors.forename: E C
authors.initials: EC
authors.lastname: Mar
authors.forename: H H
authors.initials: HH
authors.lastname: Suh
authors.forename: J S
authors.initials: JS
authors.lastname: Hong