Regulation of Nociceptin/Orphanin FQ Gene Expression by Neuropoietic Cytokines and Neurotrophic Factors in Neurons and Astrocytes

• Published in: Journal of neurochemistry 1999-05, Vol.72 (5), p.1882-1889
• Main Authors: Buzas, Beata, Symes, Aviva J., Cox, Brian M.
• Format: Article
• Language: English
• Subjects: Animals; Astrocytes; Astrocytes - physiology; Biological and medical sciences; Cerebral Cortex - cytology; Cerebral Cortex - metabolism; Ciliary Neurotrophic Factor; Corpus Striatum - cytology; Corpus Striatum - metabolism; Cytokines - pharmacology; Cytokines - physiology; DNA - metabolism; DNA-Binding Proteins - genetics; Enkephalins - genetics; Fundamental and applied biological sciences. Psychology; Gene expression regulation; Gene Expression Regulation - drug effects; Gene Expression Regulation - physiology; Inflammation Mediators - pharmacology; Isolated neuron and nerve. Neuroglia; JAK/STAT pathway; Nerve Growth Factors - pharmacology; Nerve Growth Factors - physiology; Nerve Tissue Proteins - pharmacology; Neurons; Neurons - physiology; Nociceptin; Nociceptin/orphanin FQ; Opioid Peptides - genetics; Opioid Peptides - metabolism; Protein Kinases - physiology; Protein Precursors - genetics; Rats - embryology; Receptors, Opioid, mu - genetics; RNA, Messenger - metabolism; STAT1 Transcription Factor; Trans-Activators - genetics; Vertebrates: nervous system and sense organs
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1046/j.1471-4159.1999.0721882.x

: 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.