The acute inhibitory effects of iodide excess on sodium/iodide symporter expression and activity involve the PI3K/Akt signaling pathway

SERRANO-NASCIMENTO, C; DA SILVA TEIXEIRA, ; NICOLA, JP; NACHBAR, RT; CURI, R; MASINI-REPISO, AM; NUNEZ, MT

ENDOCRINOLOGY

ENDOCRINE SOC

Año: 2014 vol. 155 p. 1145 - 1156

0013-7227

Iodide (I-) is an irreplaceable constituent of thyroid hormones and an important regulator of thyroid function, as high concentrations of I- downregulate NIS expression and function. In thyrocytes, PI3K/Akt pathway regulates NIS expression. Activation of PI3K/Akt inhibits NIS expression and function. Since I- excess and PI3K/Akt signaling share similar inhibitory effects on NIS expression, we aimed to study whether the PI3K/Akt signaling mediates the inhibitory effect of I- excess on NIS expression. Here, we reported that I- excess increased Akt phosphorylation under normal or TSH/insulin starving conditions. I- stimulated Akt phosphorylation in a PI3K-dependent manner, as PI3K inhibitors abrogated the effect of I-. Moreover, I- inhibitory effect on NIS expression and function were abolished when the PI3K/Akt signaling was blocked through specific inhibitors. 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 (DHE) and MitoSOX Red, we observed that I- excess induces ROS production, and determined the mitochondria as the source of anion superoxide. Furthermore, the ROS scavengers N-acetyl cysteine (NAC) and Ebselen blocked the effect of I- on Akt phosphorylation and NIS expression. Overall, our data demonstrated the involvement of the PI3K/Akt signaling as a novel mediator of the I--induced thyroid autoregulation, linking the role of thyroid oxidative state to the ?escape? of the Wolff-Chaikoff effect.