ROMERO JORGE MIGUEL
Congresos y reuniones científicas
Título:
NF-kappaB p65 S-nitrosylation inhibits TSH-induced Na+ /I- symporter expression
Autor/es:
NICOLA, J.P; PEYRET, V; NAZAR, M; ROMERO, J M; LUCERO, A. M; MONTESINOS, M. M.; BOCCO, J. L; PELLIZAS, C. G; MASINI-REPISO, A. M
Lugar:
Lake Buena Vista, Orlando
Reunión:
Congreso; 15th International Thyroid Congress and 85th Annual Meeting of the American Thyroid Association; 2015
Institución organizadora:
American Thyroid Association
Resumen:
Nitric oxide (NO) is a ubiquitous signaling molecule involved in a
wide variety of cellular physiological processes. In thyroid cells, NOsynthase
III-endogenously produced NO reduces thyrotropin (TSH)-
stimulated thyroid specific gene expression, suggesting a potential
autocrine role of NO in modulating thyroid function. Further studies
indicate that NO induces thyroid dedifferentiation, since NO donors
repress TSH-stimulated I- uptake. Here, we investigated the molecular
mechanism underlying the NO-inhibited Na+ /I- Symporter
(NIS)-mediated I- uptake in thyroid cells FRTL-5 cells, a line of highly differentiated rat thyroid-derived cells, were incubated with different NO donors (sodium nitroprusside,
S-nitrosoglutathione, Spermine NONOate). NIS function was
measured using 125I- transport assays, and NIS expression was
evaluated through western blot, RT/qPCR, and gene reporter assays.
NIS post-transcriptional modifications were evaluated in FRTL-5
cells stably expressing N-terminal HA-tagged NIS.
NO donors reduced I- uptake in a concentration-dependent manner,
which correlated with decreased NIS protein expression. NOreduced
I- uptake resulted from transcriptional repression of NIS
gene rather than post-transcriptional modifications impairing functional
NIS expression at the plasma membrane. We observed that NO
donors repress TSH-induced NIS gene expression by reducing the
NF-jB subunit p65-dependent transcriptional activity rather than
affecting Pax8 expression or transcriptional activity. NO-promoted
Cys-38 p65 S-nitrosylation reduces p65-mediated transactivation of
the NIS promoter in response to TSH stimulation.
We demonstrated that exogenous NO-induced p65 S-nitrosylation
repressed TSH-stimulated NIS gene transcription, thus leading to a
subsequent reduction of NIS-mediated I- uptake in rat thyrocytes.
These findings support the participation of NO as an inhibitory signal
molecule to counterbalance TSH-stimulated NF-jB activation, thus
modulating TSH-induced thyroid specific gene expression.
wide variety of cellular physiological processes. In thyroid cells, NOsynthase
III-endogenously produced NO reduces thyrotropin (TSH)-
stimulated thyroid specific gene expression, suggesting a potential
autocrine role of NO in modulating thyroid function. Further studies
indicate that NO induces thyroid dedifferentiation, since NO donors
repress TSH-stimulated I- uptake. Here, we investigated the molecular
mechanism underlying the NO-inhibited Na+ /I- Symporter
(NIS)-mediated I- uptake in thyroid cells FRTL-5 cells, a line of highly differentiated rat thyroid-derived cells, were incubated with different NO donors (sodium nitroprusside,
S-nitrosoglutathione, Spermine NONOate). NIS function was
measured using 125I- transport assays, and NIS expression was
evaluated through western blot, RT/qPCR, and gene reporter assays.
NIS post-transcriptional modifications were evaluated in FRTL-5
cells stably expressing N-terminal HA-tagged NIS.
NO donors reduced I- uptake in a concentration-dependent manner,
which correlated with decreased NIS protein expression. NOreduced
I- uptake resulted from transcriptional repression of NIS
gene rather than post-transcriptional modifications impairing functional
NIS expression at the plasma membrane. We observed that NO
donors repress TSH-induced NIS gene expression by reducing the
NF-jB subunit p65-dependent transcriptional activity rather than
affecting Pax8 expression or transcriptional activity. NO-promoted
Cys-38 p65 S-nitrosylation reduces p65-mediated transactivation of
the NIS promoter in response to TSH stimulation.
We demonstrated that exogenous NO-induced p65 S-nitrosylation
repressed TSH-stimulated NIS gene transcription, thus leading to a
subsequent reduction of NIS-mediated I- uptake in rat thyrocytes.
These findings support the participation of NO as an inhibitory signal
molecule to counterbalance TSH-stimulated NF-jB activation, thus
modulating TSH-induced thyroid specific gene expression.
