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Transcriptional activation of human mu‐opioid receptor gene by insulin‐like growth factor‐I in neuronal cells is modulated by the transcription factor REST
Author(s) -
Bedini Andrea,
Baiula Monica,
Spampinato Santi
Publication year - 2008
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2008.05303.x
Subject(s) - transcription factor , microbiology and biotechnology , response element , biology , general transcription factor , e box , repressor , transcription (linguistics) , promoter , transfection , gene expression , gene , genetics , linguistics , philosophy
The human mu‐opioid receptor gene (OPRM1) promoter contains a DNA sequence binding the repressor element 1 silencing transcription factor (REST) that is implicated in transcriptional repression. We investigated whether insulin‐like growth factor I (IGF‐I), which affects various aspects of neuronal induction and maturation, regulates OPRM1 transcription in neuronal cells in the context of the potential influence of REST. A series of OPRM1‐luciferase promoter/reporter constructs were transfected into two neuronal cell models, neuroblastoma‐derived SH‐SY5Y cells and PC12 cells. In the former, endogenous levels of human mu‐opioid receptor (hMOPr) mRNA were evaluated by real‐time PCR. IGF‐I up‐regulated OPRM1 transcription in: PC12 cells lacking REST, in SH‐SY5Y cells transfected with constructs deficient in the REST DNA binding element, or when REST was down‐regulated in retinoic acid‐differentiated cells. IGF‐I activates the signal transducer and activator of transcription‐3 signaling pathway and this transcription factor, binding to the signal transducer and activator of transcription‐1/3 DNA element located in the promoter, increases OPRM1 transcription. We propose that a reduction in REST is a critical switch enabling IGF‐I to up‐regulate hMOPr. These findings help clarify how hMOPr expression is regulated in neuronal cells.