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

Autor(es)

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]

Afiliação do(s) autor(es)

^[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

• Tipo de documento: Artigo Científico
• Fonte: Life Sciences; v. 94, n. 2, p. 122-129, JAN 17 2014.
• Citações Web of Science: 11

Resumo

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)

• Processo FAPESP: 04/04328-1 - Sintese de melatonina na glandula pineal de ratos: modulacao pelo glutamato.
• Beneficiário: Solange Castro Afeche
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 05/56943-4 - Sinalizacao intracelular glutamatergica e sintese de melatonina na glandula pineal de ratos: influencia do oxido nitrico e dos fatores de transcricao nf-kb e creb.
• Beneficiário: Darine Christina Maia Villela
• Modalidade de apoio: Bolsas no Brasil - Mestrado