S-Nitrosylation of NF-B p65 Inhibits TSH-Induced Na/I Symporter Expression

NICOLA JP; PEYRET V; NAZAR, M; ROMERO, JM; LUCERO, AM; MONTESINOS, MM; BOCCO, JL; PELLIZAS, CG; MASINI-REPISO AM

ENDOCRINOLOGY

ENDOCRINE SOC

Año: 2015 vol. 156 p. 4741 - 4754

0013-7227

Nitric oxide (NO) is a ubiquitous signaling molecule involved in a wide variety of cellular physiological processes. In thyroid cells, NO-synthase III-endogenously produced NO reduces TSH-stimulated thyroid-specific gene expression, suggesting a potential autocrine role ofNOin modulating thyroid function. Further studies indicate that NO induces thyroid dedifferentiation, because NO donors repress TSH-stimulated iodide (I) uptake. Here, we investigated the molecular mechanismunderlying the NO-inhibited Na/I symporter (NIS)-mediated I uptake in thyroid cells. We showed that NO donors reduce I uptake in a concentration-dependent manner, which correlates with decreased NIS protein expression. NO-reduced I uptake results from transcriptional repression of NIS gene rather than posttranslational modifications reducing functional NIS expression at the plasma membrane. We observed that NO donors repress TSH-induced NIS gene expression by reducing the transcriptional activity of the nuclear factor-B subunit p65. NO-promoted p65 Snitrosylation reduces p65-mediated transactivation of the NIS promoter in response to TSH stimulation. Overall, our data are consistent with the notion that NO plays a role as an inhibitory signal to counterbalance TSH-stimulated nuclear factor-B activation, thus modulating thyroid hormone biosynthesis.