S-Nitrosylation of NF-kB p65 Inhibits TSH-Induced Na(+)/I(-) Symporter Expression.

JUAN PABLO NICOLA*; VICTORIA PEYRET*; MAGALÍ NAZAR; JORGE MIGUEL ROMERO; ARIEL MAXIMILIANO LUCERO; MARÍA DEL MAR MONTESINOS; JOSÉ LUIS BOCCO; CLAUDIA GABRIELA PELLIZAS; ANA MARÍA MASINI-REPISO

ENDOCRINOLOGY

ENDOCRINE SOC

Año: 2015

0013-7227

itric oxide (NO) is a ubiquitous signaling molecule involved in a wide variety of cellular physiologicalprocesses. In thyroid cells, NO-synthase III-endogenously produced NO reduces TSH-stimulatedthyroid-specific gene expression, suggesting a potential autocrine role of NO in modulatingthyroid function. Further studies indicate that NO induces thyroid dedifferentiation, because NOdonors 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. Weshowed that NO donors reduce I uptake in a concentration-dependent manner, which correlateswith decreased NIS protein expression. NO-reduced I uptake results from transcriptional repressionof NIS gene rather than posttranslational modifications reducing functional NIS expression atthe plasma membrane. We observed that NO donors repress TSH-induced NIS gene expression byreducing the transcriptional activity of the nuclear factor-B s