Excess iodide downregulates Na+/I- symporter gene transcription through activation of PI3K/Akt pathway

Author(s)

Serrano-Nascimento, Caroline ^[1] ; Pablo Nicola, Juan ^[2] ; Teixeira, Silvania da Silva ^[1] ; Poyares, Leonice Lourenco ^[1] ; Lellis-Santos, Camilo ^[3] ; Bordin, Silvana ^[1] ; Maria Masini-Repiso, Ana ^[2] ; Nunes, Maria Tereza ^[1]

Affiliation

^[1] Univ Sao Paulo, Inst Biomed Sci, Dept Physiol & Biophys, BR-05508000 Sao Paulo - Brazil

^[2] Univ Nacl Cordoba, Fac Ciencias Quim, Dept Bioquim Clin, Ctr Invest Bioquim Clin & Inmunol, RA-5000 Cordoba - Argentina

^[3] Univ Fed Sao Paulo, Inst Environm Chem & Pharmaceut Sci, Dept Biol Sci, Sao Paulo - Brazil

• Document type: Journal article
• Source: Molecular and Cellular Endocrinology; v. 426, n. C, p. 73-90, MAY 5 2016.
• Web of Science Citations: 10

Abstract

Transcriptional mechanisms associated with iodide-induced downregulation of NIS expression remain uncertain. Here, we further analyzed the transcriptional regulation of NIS gene expression by excess iodide using PCCl3 cells. NIS promoter activity was reduced in cells treated for 12-24 h with 10(-5) to 10(-3) M NaI. Site-directed mutagenesis of Pax8 and NF-kappa B cis-acting elements abrogated the iodide induced NIS transcription repression. Indeed, excess iodide (10(-3) M) excluded Pax8 from the nucleus, decreased p65 total expression and reduced their transcriptional activity. Importantly, p65-Pax8 physical interaction and binding to NIS upstream enhancer were reduced upon iodide treatment. PI3K/Akt pathway activation by iodide-induced ROS production is involved in the transcriptional repression of NIS expression. In conclusion, the results indicated that excess iodide transcriptionally represses NIS gene expression through the impairment of Pax8 and p65 transcriptional activity. Furthermore, the data presented herein described novel roles for PI3K/Akt signaling pathway and oxidative status in the thyroid autoregulatory phenomenon. 2016 Elsevier Ireland Ltd. All rights reserved. (AU)

• FAPESP's process: 09/17834-6 - Study of the molecular basis of the short-term regulation of the Na+/I- symporter (NIS) and pendrin gene expression in rats thyroid and PCCl3 cells: possible contribution to the comprehension of the Wolff-Chaikoff effect and the escape phenomenon
• Grantee: Maria Tereza Nunes
• Support Opportunities: Regular Research Grants