Serotonin 1A receptor coupling to NF-κB studied using inducible receptor expression in hippocampal neuron-derived cells

Tomasz Sobocki, Indrani Ray, Patricia Cano-Sanchez, Probal Banerjee, Efrain C. Azmitia

Research output: Contribution to journalArticle

Abstract

The mechanism of serotonin 1A receptor (5-HT1A-R) mediated activation of NF-κB has been studied in non-neural cells, but this pathway has not been elucidated in neuronal cells. We have used inducible expression of the 5-HT1A-R in the hippocampal neuron-derived HN2 cells to analyze the coupling of this receptor to NF-κB. A construct harboring luciferase cDNA driven by a minimal promoter under the control of an NF-κB-specific enhancer element was transfected into these 5-HT1A-R-expressing HN2 cells. Using luciferase expression in the transfected cells, we have studied 5-HT1A-R agonist evoked activation of NF-κB. Inhibition of either mitogen activated protein kinase (MAPK) pathway with PD98059 or protein kinase C (PKC) with GFX caused elevation of the basal level of NF-κB activity but did not affect 5-HT1A-R mediated activation of NF-κB. Furthermore, neither the basal level of NF-κB nor its activation by a 5-HT1A-R agonist was altered by dibutyrylcAMP. Thus, the MAPK pathway and PKC cause inhibition of the basal NF-κB activity and the 5-HT1A-R-linked NF-κB activation does not require MAPK, PKC, and cAMP. Intriguingly, Western blot analysis showed that 5-HT 1A-R mediates activation of both CaMKII and PI-3K. This 5-HT 1A-R-evoked the stimulation of CaMKII was reversed in the presence of a PI-3K inhibitor. Therefore, the likely mechanism of 5-HT1A-R mediated induction of NF-κB in neuronal cells involves activation of PI-3K upstream of CaMKII. This reveals a novel pathway that could be crucial in the functional activity of brain neurons.

Original languageEnglish (US)
Pages (from-to)260-269
Number of pages10
JournalSignal Transduction
Volume7
Issue number3
DOIs
StatePublished - 2007

Keywords

  • 5-HT receptor
  • Hippocampal neuron
  • Inducible expression
  • Luciferase reporter
  • NF-κB

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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