17β-estradiol-induced regulation of the novel 5-HT1A-related transcription factors NUDR and Freud-1 in SH SY5Y cells.
Nuclear deformed epidermal autoregulatory factor-1 (NUDR/Deaf-1) and five prime repressor element under dual repression (Freud-1) are novel transcriptional regulators of the 5-HT(1A) receptor, a receptor that has been implicated in the pathophysiology of various psychiatric illnesses. The antidepressant effect of 17β-Estradiol (17βE(2)) is purported to involve the downregulation of this receptor. We investigated the possible role of NUDR and Freud-1 in 17βE(2)-induced downregulation of the 5-HT(1A) receptor in the neuroblastoma cell line SH SY5Y. Cells were treated with 10 nM of 17βE(2) for 3 or 48 h, followed by a 24-h withdrawal period. Proteins were isolated and analyzed by western blotting. 17βE(2) treatment increased NUDR immunoreactivity while Freud-1 and the 5-HT(1A) receptor showed significant decreases. Upon withdrawal of 17βE(2), protein expression returned to control levels, except for NUDR, which remained significantly elevated in the 3-h treatment. Taken together, these data support a non-genomic downregulation of 5-HT(1A) receptor protein by 17βE(2), which does not involve NUDR and Freud-1. Rather, changes in both transcription factors seem to be compensatory/homeostatic responses to changes in 5-HT(1A) receptor induced by 17βE(2). These observations further highlight the importance of NUDR and Freud-1 in regulating 5-HT(1A) receptor expression.
Graduate Program in Neuroscience, School of Graduate Studies in the Health Sciences, University of Mississippi Medical Center, Jackson, MS 39216-4505, USA.
Samuel O
SO
Adeosun
Paul R
PR
Albert
Mark C
MC
Austin
Abiye H
AH
Iyo
D015415:Biomarkers / Q000378:metabolism; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D003866:Depressive Disorder / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D004958:Estradiol / Q000502:physiology*; D006801:Humans; D009447:Neuroblastoma; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D044282:Receptor, Serotonin, 5-HT1A / Q000235:genetics*; D014157:Transcription Factors
D015415:Biomarkers; C512283:CC2D1A protein, human; C116013:DEAF1 protein, human; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; D044282:Receptor, Serotonin, 5-HT1A; D004958:Estradiol