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Journal of Neuroscience, Vol 16, 919-929, Copyright © 1996 by Society for Neuroscience
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
JR Cardinaux and PJ Magistretti
Laboratoire de Recherche Neurologique, Institut de Physiologie et Service de Neurologie du CHUV, Faculte de Medecine, Universite de Lausanne, Switzerland.
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.
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