Regulation of nociceptin/orphanin FQ gene expression by neuropoietic cytokines and neurotrophic factors in neurons and astrocytes.
We have identified the gene encoding nociceptin/orphanin FQ (N/OFQ), the novel opioid-like neuropeptide, as responsive to ciliary neurotrophic factor (CNTF). N/OFQ mRNA levels were induced five- and ninefold by CNTF in striatal and cortical neurons. In primary astrocytes CNTF also increased N/OFQ mRNA levels. CNTF is a multifunctional cytokine that mediates the development and differentiation of both neurons and astrocytes and supports the survival of various neurons. CNTF is also an injury-induced factor in the brain playing a crucial role in astrogliosis. The mechanism by which CNTF elicits these effects is not well understood, but it is likely to involve regulation of specific genes. CNTF regulation of N/OFQ expression was sensitive to the kinase inhibitors H-7 and genistein but not to inhibition of protein synthesis. This pharmacological profile is consistent with CNTF activating the Janus protein tyrosine kinase (JAK)/ signal transducers and activators of transcription (STAT) pathway to induce N/OFQ transcription. In nuclear extracts of CNTF-treated striatal neurons DNA binding of STAT proteins was increased. Radioimmunoassays revealed elevated N/OFQ immunoreactivity in striatal neurons after CNTF treatment. Expression of the related proenkephalin gene was not affected by CNTF in either neuronal or glial cultures. Regulation of N/OFQ expression by CNTF might point to a possible function of N/OFQ during development and after neural injury.
Buzas
B
B
Department of Pharmacology, Uniformed Services University, Bethesda, Maryland 20814, USA.
Symes
A J
AJ
Cox
B M
BM
D000818:Animals; D001253:Astrocytes / Q000502:physiology*; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism; D020934:Ciliary Neurotrophic Factor; D003342:Corpus Striatum / Q000166:cytology / Q000378:metabolism; D016207:Cytokines / Q000494:pharmacology / Q000502:physiology*; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics; D004745:Enkephalins / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D018836:Inflammation Mediators / Q000494:pharmacology; D009414:Nerve Growth Factors / Q000494:pharmacology / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000494:pharmacology; D009474:Neurons / Q000502:physiology*; D018847:Opioid Peptides / Q000235:genetics* / Q000378:metabolism; D011494:Protein Kinases / Q000502:physiology; D011498:Protein Precursors / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats / Q000196:embryology; D017450:Receptors, Opioid, mu / Q000235:genetics; D050794:STAT1 Transcription Factor; D015534:Trans-Activators / Q000235:genetics; D000097629:Nociceptin
D020934:Ciliary Neurotrophic Factor; D016207:Cytokines; D004247:DNA; D004268:DNA-Binding Proteins; D004745:Enkephalins; D018836:Inflammation Mediators; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D018847:Opioid Peptides; D011494:Protein Kinases; D011498:Protein Precursors; D012333:RNA, Messenger; D017450:Receptors, Opioid, mu; D050794:STAT1 Transcription Factor; D015534:Trans-Activators; D000097629:Nociceptin; C029992:proenkephalin