Identification of nuclear factor-kappa B sites in the Slc2a4 gene promoter

Autor(es)

Furuya, D. T. ^[1] ; Neri, E. A. ^[1] ; Poletto, A. C. ^[1] ; Anhe, G. F. ^[2] ; Freitas, H. S. ^[1] ; Campello, R. S. ^[1] ; Reboucas, N. A. ^[1] ; Machado, U. F. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Dept Physiol & Biophys, Inst Biomed Sci, BR-05508900 Sao Paulo - Brazil

^[2] Univ Estadual Campinas, Dept Pharmacol, Fac Med Sci, Campinas, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Molecular and Cellular Endocrinology; v. 370, n. 1-2, p. 87-95, MAY 6 2013.
• Citações Web of Science: 17

Resumo

Glucose transporter GLUT4 protein, codified by Slc2a4 gene plays a key role in glycemic homeostasis. Insulin resistance, as in obesity, has been associated to inflammatory state, in which decreased GLUT4 is a feature. Inflammatory NF-kappa B transcriptional factor has been proposed as a repressor of Slc2a4; although, the binding site(s) in Slc2a4 promoter and the direct repressor effect have never been reported yet. A motif-based sequence analysis of mouse Slc2a4 promoter revealed two putative kappa B sites located inside -83/-62 and -134/-113 bp. Eletrophoretic mobility assay showed that p50 and p65 NF-kappa B subunits bind to both putative kappa B sites. Chromatin immunoprecipitation assay using genomic DNA from adipocytes confirmed p50- and p65-binding to Slc2a4 promoter. Moreover, transfection experiments revealed that NF-kappa B binds to the -134/-113 bp region of the mouse Slc2a4 gene promoter, inhibiting the Slc2a4 gene transcription. The current findings demonstrate the existence of two kappa B sites in Slc2a4 gene promote, and that NF-kappa B has a direct repressor effect upon the Slc2a4 gene, providing an important link between insulin resistance and inflammation. (C) 2013 Elsevier Ireland Ltd. All rights reserved. (AU)

• Processo FAPESP: 07/50554-1 - Transportadores de glicose e Diabetes mellitus: contribuição ao conhecimento da regulação da glicemia e do desenvolvimento de complicações
• Beneficiário: Ubiratan Fabres Machado
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 11/08570-5 - Regulação da expressão do gene SLC2A4 pelo fator de transcrição nuclear factor NF-Kappa B (NF-kB): controle direto da atividade ranscricional?
• Beneficiário: Ubiratan Fabres Machado
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 08/09194-4 - Modulação da proteína transportadora de glicose glut4 pelo receptor canabinóide cb1 em adipócitos 3t3-l1 e tecido adiposo visceral de camungos obesos
• Beneficiário: Daniela Tomie Furuya
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado