Participation of the transcription factor SP1 in estradiolinduced regulation of Slc2a4/GLUT4 expression in adipocytes 3T3L1

• Grant number: 15/18715-1
• Support Opportunities: Scholarships in Brazil - Master
• Effective date (Start): March 01, 2016
• Effective date (End): February 28, 2018
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Ubiratan Fabres Machado
• Grantee: João Nilton Barreto Andrade
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 12/04831-1 - New players in glycemic control and chronic complications of Diabetes mellitus: preventive and therapeutic perspectives, AP.TEM

Abstract

Insulin resistance (IR) is characterized by a reduction in the ability of insulin sensitive tissues respond appropriately to normal concentrations of the hormone. Changes in the expression of the insulin-sensitive glucose transporter GLUT4 (encoded by the gene Slc2a4) play a fundamental role in triggering the RI. Besides its role in female reproductive's physiology, estradiol (E2) also acts on the regulation of many other functions in males. E2, via their receptors ESR1 and ESR2, regulates gene expression by direct DNA binding or by interaction with other transcription factors, including SP1 (Specificity Protein 1). Researches have shown that Slc2a4 has four binding sites for SP1 in its promoter region, suggesting that the regulation of the Slc2a4 expression by E2 can involve the protein SP1. Thus, the purpose of this study is to evaluate the role of SP1 in the expression of Slc2a4/GLUT4 mediated by estradiol in adipocyte cell line 3T3-L1, seeking to understand the role of both estradiol receptors in this regulation. For that, 3T3-L1 adipocytes will be treated (24 hours) with E2 and/or ESRs selective agonists, and thus processed for the following analyzes: Western blotting for quantification of the proteins GLUT4 and SP1; Real-time PCR to assess the expression of the genes Slc2a4 and Sp1; Immunoprecipitation for evaluation of the interaction SP1-ESR1/2. The present study expects to demonstrate the effect of SP1 on the modulation of Slc2a4 expression induced by E2 in adipocytes, contributing to the elucidation of mechanisms involved in insulin resistance and consequently in the control of glucose homeostasis.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

BARRETO-ANDRADE, JOAO NILTON; DE FATIMA, LUCIANA ALVES; CAMPELLO, RAQUEL SALDANHA; CIPRIANO GUEDES, JOSE AUGUSTO; DE FREITAS, HELAYNE SOARES; UBIRATAN FABRES MACHADO, MARISTELA MITIKO OKAMOTO. Estrogen Receptor 1 (ESR1) Enhances Slc2a4/GLUT4 Expression by a SP1 Cooperative Mechanism. INTERNATIONAL JOURNAL OF MEDICAL SCIENCES, v. 15, n. 12, p. 1320-1328, 2018. (16/15603-0, 15/18715-1)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

ANDRADE, João Nilton Barreto. SP1 (transcription factor Sp1) participates in the transcriptional regulation of Slc2a4 mediated by estrogen receptor ER-alpha in 3T3-L1 adipocytes. 2018. Master's Dissertation - Universidade de São Paulo (USP). Faculdade de Medicina (FM/SBD) São Paulo.