S-nitrosylation of NFkB p65 inhibits TSH-induced Na+/I- symporter expression

NICOLA JP; PEYRET V; NAZAR M; MONTESINOS MM; LUCERO AM; PELLIZAS CG; MASINI-REPISO AM

ENDOCRINE SOC

Año: 2015 vol. 146 p. 4741 - 4741

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 ofNOin 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 sub