The Acute Inhibitory Effect of Iodide Excess on Sodium/Iodide Symporter Expression and Activity Involves the PI3K/Akt Signaling Pathway
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 (A...
| Autores: | , , , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2014 |
| País: | Argentina |
| Institución: | Consejo Nacional de Investigaciones Científicas y Técnicas |
| Repositorio: | CONICET Digital (CONICET) |
| Idioma: | inglés |
| OAI Identifier: | oai:ri.conicet.gov.ar:11336/31871 |
| Acceso en línea: | http://hdl.handle.net/11336/31871 |
| Access Level: | acceso abierto |
| Palabra clave: | Sodium-Iodide Symporter (Nis) Pi3k/Akt Cascade Reactive Oxygen Species (Ros) Thyroid Autoregulation https://purl.org/becyt/ford/3.1 https://purl.org/becyt/ford/3 |
| Sumario: | 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− excess on 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 (Akt1/2 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 production in 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. |
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