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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.)

The Acute Inhibitory Effect of Iodide Excess on Sodium/Iodide Symporter Expression and Activity Involves the PI3K/Akt Signaling Pathway

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Author(s):
Serrano-Nascimento, Caroline [1] ; Teixeira, Silvania da Silva [1] ; Pablo Nicola, Juan [2] ; Nachbar, Renato Tadeu [1] ; Maria Masini-Repiso, Ana [2] ; Nunes, Maria Tereza [1]
Total Authors: 6
Affiliation:
[1] Univ Sao Paulo, Dept Physiol & Biophys, Inst Biomed Sci, BR-05508000 Sao Paulo - Brazil
[2] Univ Nacl Cordoba, Fac Ciencias Quim, Dept Bioquim Clin, Ctr Invest Bioquim Clin & Inmunol, Consejo Nacl In, RA-5000 Cordoba - Argentina
Total Affiliations: 2
Document type: Journal article
Source: Endocrinology; v. 155, n. 3, p. 1145-1156, MAR 2014.
Web of Science Citations: 48
Abstract

Iodide (I-) is an irreplaceable constituent of thyroid hormones and an important regulator of thyroid function, because high concentrations of I- down-regulate sodium/iodide symporter (NIS) expression and function. In thyrocytes, activation of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) cascade also inhibits NIS expression and function. Because I- excess and PI3K/Akt signaling pathway induce similar inhibitory effects on NIS expression, we aimed to study whether the PI3K/Akt cascade mediates the acute and rapid inhibitory effect of I- excesson NIS expression/activity. Here, we reported that the treatment of PCCl3 cells with I- excess increased Akt phosphorylation under normal or TSH/insulin-starving conditions. I- stimulated Akt phosphorylation in a PI3K-dependent manner, because the use of PI3K inhibitors (wortmannin or 2-(4-Morpholinyl)-8-phenyl-4H-1-benzopyran-4-one) abrogated the induction of I- effect. Moreover, I- inhibitory effect on NIS expression and function were abolished when the cells were previously treated with specific inhibitors of PI3K or Akt (Akt 1/2 kinase inhibitor). Importantly, we also found that the effect of I- on NIS expression involved the generation of reactive oxygen species (ROS). Using the fluorogenic probes dihydroethidium and mitochondrial superoxide indicator (MitoSOX Red), we observed that I- excess increased ROS productionin thyrocytes and determined that mitochondria were the source of anion superoxide. Furthermore, the ROS scavengers N-acetyl cysteine and 2-phenyl-1,2-benzisoselenazol-3-(2H)-one blocked the effect of I- on Akt phosphorylation. Overall, our data demonstrated the involvement of the PI3K/Akt signaling pathway as a novel mediator of the I--induced thyroid autoregulation, linking the role of thyroid oxidative state to the Wolff-Chaikoff effect. (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 type: Regular Research Grants