title: Regulation of the prepronociceptin gene and its effect on neuronal differentiation.
abstract: Nociceptin/orphanin FQ (NOP/OFQ) is the endogenous ligand for the NOP receptor and is processed from a precursor protein in the family of opioid peptides. Prepronociceptin (ppN/OFQ) mRNA has been shown to be upregulated by an increase in cAMP, a treatment that leads to differentiation of NS20Y neuroblastoma cells. Although a large increase in endogenous ppN/OFQ mRNA upon cAMP stimulation can be shown in cellular systems, a similar increase cannot be expressed in pGL3 luciferase vector containing 1.3 kb proximal promoter, suggesting that a larger portion of the sequence or a different chromatin structure is necessary for a fully functional promoter. The induction of ppN/OFQ mRNA by cAMP appears to be mediated by a cAMP-response element. Chromatin immunoprecipitation (ChIP) assays show that CREB is recruited to the promoter region upon treatment of NS20Y cells with dibutyryl cAMP. In addition, the production of ppN/OFQ mRNA is regulated by histone acetylation, also through CREB, as the histone deacetylase (HDAC) inhibitor trichostatin A increases both CREB binding to the promoter and ppN/OFQ mRNA expression. In rat progenitor and mouse neuroblastoma cell lines, agents that increase ppN/OFQ mRNA expression also induce neurite outgrowth, suggesting a close relationship between ppN/OFQ and cellular differentiation.
authors.affiliation: SRI International, Biosciences Division, 333 Ravenswood Ave, LA214A, Menlo Park, CA 94025, USA. naunihal.zaveri@sri.com
authors.forename: Naunihal T
authors.initials: NT
authors.lastname: Zaveri
authors.forename: Nahid
authors.initials: N
authors.lastname: Waleh
authors.forename: Lawrence
authors.initials: L
authors.lastname: Toll
mesh_terms: D000818:Animals; D001483:Base Sequence; D003994:Bucladesine / Q000494:pharmacology; D002454:Cell Differentiation; D002460:Cell Line; D047369:Chromatin Immunoprecipitation; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D005333:Fetus / Q000166:cytology; D018507:Gene Expression Regulation, Developmental; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D051379:Mice; D008969:Molecular Sequence Data; D009474:Neurons / Q000166:cytology*; D018847:Opioid Peptides / Q000235:genetics* / Q000378:metabolism; D008926:Plicamycin / Q000031:analogs & derivatives / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D011498:Protein Precursors / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011957:Receptors, Opioid / Q000235:genetics* / Q000378:metabolism; D016415:Sequence Alignment; D013449:Sulfonamides / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection; D000097629:Nociceptin
chemical_list: D003994:Bucladesine; D017362:Cyclic AMP Response Element-Binding Protein; D006877:Hydroxamic Acids; D007546:Isoquinolines; D018847:Opioid Peptides; D008926:Plicamycin; D011498:Protein Precursors; D011957:Receptors, Opioid; D013449:Sulfonamides; D000097629:Nociceptin; C121527:prepronociceptin; C012589:trichostatin A; C066851:mithramycin A; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide