Vasoactive intestinal peptide, pituitary adenylate cyclase-activating peptide, and noradrenaline induce the transcription factors CCAAT/enhancer binding protein (C/EBP)-β and C/EBPδ in mouse cortical astrocytes: Involvement in cAMP-regulated glycogen metabolism

Abstract

We have described previously a transcription-dependent induction of glycogen resynthesis by the vasoactive intestinal peptide (VIP) or noradrenaline (NA) in astrocytes, which is mediated by cAMP. Because it has been postulated that the cAMP-mediated regulation of energy balance in hepatocytes and adipocytes is channeled at least in part through the CCAAT/enhancer binding protein (C/EBP) family of transcription factors, we tested the hypothesis that C/EBP isoforms could be expressed in mouse cortical astrocytes and that their level of expression could be regulated by VIP, by the VIP-related neuropeptide pituitary adenylate cyclase-activating peptide (PACAP), or by NA. We report in this study that in these cells, C/EBPβ and C/EBPδ are induced by VIP, PACAP, or NA via the cAMP second-messenger pathway. Induction of C/EBPβ and -δ mRNA by VIP occurs in the presence of a protein synthesis inhibitor. Thus, c/ebpβ and c/ebpδ behave as cAMP-inducible immediate-early genes in astrocytes. Moreover, transfection of astrocytes with expression vectors selectively producing the transcriptionally active form of C/EBPβ, termed liver-enriched transcriptional activator protein, or C/EBPδ enhance the glycogen resynthesis elicited by NA, whereas an expression vector producing the transcriptionally inactive form of C/EBPβ, termed liver-enriched transcriptional inhibitory protein, reduces this resynthesis. These results support the idea that C/EBPβ and -δ regulate gene expression of energy metabolism-related enzymes in astrocytes.