Norepinephrine activates NF-kappa B transcription factor in cultured rat pineal gland

作者：Villela Darine; Lima Larissa de Sa; Peres Rafael; Peliciari Garcia Rodrigo Antonio; do Amaral Fernanda Gaspar; Cipolla Neto Jose; Scavone Cristoforo; Afeche Solange Castro^*

来源：Life Sciences, 2014, 94(2): 122-129.

DOI：10.1016/j.lfs.2013.11.004

• Pineal gland
• Norepinephrine
• NF-kappa B
• Melatonin
• Aanat transcription
• AANAT activity

Aims: The circadian rhythm in mammalian pineal melatonin secretion is modulated by norepinephrine (NE) released at night. NE interaction with beta(1)-adrenoceptors activates PKA that phosphorylates the transcription factor CREB, leading to the transcription and translation of the arylalkylamine-N-acetyltransferase (AANAT) enzyme. Several studies have reported the interplay between CREB and the nuclear factor-kappa B (NF-kappa B) and a circadian rhythm for this transcription factor was recently described in the rat pineal gland. In this work we studied a direct effect of NE on NF-kappa B activation and the role played by this factor on melatonin synthesis and Aanat transcription and activity.
Main methods: Cultured rat pineal glands were incubated in the presence of two different NF-kappa B inhibitors, pyrrolidine-dithiocarbamate or sodium salicylate, and stimulated with NE. Melatonin content was quantified by HPLC with electrochemical detection. AANAT activity was measured by a radiometric assay and the expression of Aanat mRNA was analyzed by real-time PCR. Gel shift assay was performed to study the NF-kappa B activation in cultured rat pineal glands stimulated by NE.
Key findings: Our results showed that the p50/p50 homodimer of NF-kappa B is activated by NE and that it has a role in melatonin synthesis, acting on Aanat transcription and activity.
Significance: Here we present evidence that NF-kappa B is an important transcription factor that acts, directly or indirectly, on Aanat transcription and activity leading to a modulation of melatonin synthesis. NE plays a role in the translocation of NF-kappa B p50/p50 homodimer to the nucleus of pinealocytes, thus probably influencing the nocturnal pineal melatonin synthesis.

• 出版日期2014-1-17