Vasoactive intestinal peptide, pituitary adenylate cyclase-activating peptide, and noradrenaline induce the transcription factors CCAAT/enhancer binding protein (C/EBP)-beta and C/EBP delta in mouse cortical astrocytes: involvement in cAMP-regulated glycogen metabolism.
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/EBP beta and C/EBP delta are induced by VIP, PACAP, or NA via the cAMP second-messenger pathway. Induction of C/EBP beta and -delta mRNA by VIP occurs in the presence of a protein synthesis inhibitor. Thus, c/ebp beta and c/ebp delta behave as cAMP-inducible immediate-early genes in astrocytes. Moreover, transfection of astrocytes with expression vectors selectively producing the transcriptionally active form of C/EBP beta, termed liver-enriched transcriptional activator protein, or C/EBP delta enhance the glycogen resynthesis elicited by NA, whereas an expression vector producing the transcriptionally inactive form of C/EBP beta, termed liver-enriched transcriptional inhibitory protein, reduces this resynthesis. These results support the idea that C/EBP beta and -delta regulate gene expression of energy metabolism-related enzymes in astrocytes.
Cardinaux
J R
JR
Laboratoire de Recherche Neurologique, Institut de Physiologie et Service de Neurologie du CHUV, Faculté de Médecine, Université de Lausanne, Switzerland.
Magistretti
P J
PJ
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D000841:Anisomycin / Q000494:pharmacology; D001253:Astrocytes / Q000187:drug effects* / Q000502:physiology; D051743:CCAAT-Enhancer-Binding Protein-delta; D022762:CCAAT-Enhancer-Binding Proteins; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D004734:Energy Metabolism / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects*; D017781:Genes, Immediate-Early; D006003:Glycogen / Q000378:metabolism*; D016350:Leucine Zippers / Q000235:genetics; D051379:Mice; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D009479:Neuropeptides / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology*; D009687:Nuclear Proteins / Q000096:biosynthesis* / Q000235:genetics; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D015290:Second Messenger Systems / Q000187:drug effects / Q000502:physiology; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects*; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*
C495402:Adcyap1 protein, mouse; D022762:CCAAT-Enhancer-Binding Proteins; C497253:Cebpd protein, mouse; D004268:DNA-Binding Proteins; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D009687:Nuclear Proteins; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D011500:Protein Synthesis Inhibitors; D014157:Transcription Factors; D051743:CCAAT-Enhancer-Binding Protein-delta; D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate; D014660:Vasoactive Intestinal Peptide; D000841:Anisomycin; D006003:Glycogen; D000242:Cyclic AMP; D009638:Norepinephrine