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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Author(s):
Villela, Darine [1, 2] ; Lima, Larissa de Sa [3] ; Peres, Rafael [1] ; Peliciari-Garcia, Rodrigo Antonio [1] ; do Amaral, Fernanda Gaspar [1] ; Cipolla-Neto, Jose [1] ; Scavone, Cristoforo [3] ; Afeche, Solange Castro [2]
Total Authors: 8
Affiliation:
[1] Univ Sao Paulo, Inst Biomed Sci, Dept Physiol & Biophys, Sao Paulo - Brazil
[2] Butantan Inst, Pharmacol Lab, BR-05503900 Sao Paulo - Brazil
[3] Inst Biomed Sci, Dept Pharmacol, Mol Neuropharmacol Lab, Sao Paulo - Brazil
Total Affiliations: 3
Document type: Journal article
Source: Life Sciences; v. 94, n. 2, p. 122-129, JAN 17 2014.
Web of Science Citations: 11
Abstract

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. (C) 2013 Elsevier Inc All rights reserved. (AU)