Characterization of small-molecule inhibitors of the sodium iodide symporter

Sabine Lindenthal, Nathalie Lecat-Guillet, Alejandro Ondo-Mendez, Yves Ambroise, Bernard Rousseau, Thierry Pourcher

Resultado de la investigación: Contribución a RevistaArtículo

11 Citas (Scopus)

Resumen

The sodium/iodide symporter (NIS) mediates the active transport of iodide from the bloodstream into thyrocytes. NIS function is strategic for the diagnosis and treatment of various thyroid diseases. In addition, a promising anti-cancer strategy based on targeted NIS gene transfer in non-thyroidal cells is currently developed. However, only little information is available concerning the molecular mechanism of NIS-mediated iodide translocation. Ten small molecules have recently been identified using a high-throughput screening method for their inhibitory effect on iodide uptake of NIS-expressing mammalian cells. In the present study, we analyzed these compounds for their rapid and reversible effects on the iodide-induced current in NIS-expressing Xenopus oocytes. Four molecules almost completely inhibited the iodide-induced current; for three of them the effect was irreversible, for one compound the initial current could be fully re-established after washout. Three molecules showed a rapid inhibitory effect of about 75%, half of which was reversible. Another three compounds inhibited the iodide-induced current from 10 to 50%. Some molecules altered the membrane conductance by themselves, i.e. in the absence of iodide. For one of these molecules the observed effect was also found in water-injected oocytes whereas for some others the iodide-independent effect was associated with NIS expression. The tested molecules show a surprisingly high variability in their possible mode of action, and thus are promising tools for further functional characterization of NIS on a molecular level, and they could be useful for medical applications. © 2009 Society for Endocrinology.
Idioma originalEnglish (US)
Páginas (desde-hasta)357-365
Número de páginas9
PublicaciónJournal of Endocrinology
Volumen200
N.º3
DOI
EstadoPublished - jun 24 2009
Publicado de forma externa

Huella dactilar

Iodides
Oocytes
High-Throughput Screening Assays
sodium-iodide symporter
Active Biological Transport
Thyroid Diseases
Xenopus
Membranes
Water
Genes

Citar esto

Lindenthal, S., Lecat-Guillet, N., Ondo-Mendez, A., Ambroise, Y., Rousseau, B., & Pourcher, T. (2009). Characterization of small-molecule inhibitors of the sodium iodide symporter. Journal of Endocrinology, 200(3), 357-365. https://doi.org/10.1677/JOE-08-0246
Lindenthal, Sabine ; Lecat-Guillet, Nathalie ; Ondo-Mendez, Alejandro ; Ambroise, Yves ; Rousseau, Bernard ; Pourcher, Thierry. / Characterization of small-molecule inhibitors of the sodium iodide symporter. En: Journal of Endocrinology. 2009 ; Vol. 200, N.º 3. pp. 357-365.
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abstract = "The sodium/iodide symporter (NIS) mediates the active transport of iodide from the bloodstream into thyrocytes. NIS function is strategic for the diagnosis and treatment of various thyroid diseases. In addition, a promising anti-cancer strategy based on targeted NIS gene transfer in non-thyroidal cells is currently developed. However, only little information is available concerning the molecular mechanism of NIS-mediated iodide translocation. Ten small molecules have recently been identified using a high-throughput screening method for their inhibitory effect on iodide uptake of NIS-expressing mammalian cells. In the present study, we analyzed these compounds for their rapid and reversible effects on the iodide-induced current in NIS-expressing Xenopus oocytes. Four molecules almost completely inhibited the iodide-induced current; for three of them the effect was irreversible, for one compound the initial current could be fully re-established after washout. Three molecules showed a rapid inhibitory effect of about 75{\%}, half of which was reversible. Another three compounds inhibited the iodide-induced current from 10 to 50{\%}. Some molecules altered the membrane conductance by themselves, i.e. in the absence of iodide. For one of these molecules the observed effect was also found in water-injected oocytes whereas for some others the iodide-independent effect was associated with NIS expression. The tested molecules show a surprisingly high variability in their possible mode of action, and thus are promising tools for further functional characterization of NIS on a molecular level, and they could be useful for medical applications. {\circledC} 2009 Society for Endocrinology.",
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Lindenthal, S, Lecat-Guillet, N, Ondo-Mendez, A, Ambroise, Y, Rousseau, B & Pourcher, T 2009, 'Characterization of small-molecule inhibitors of the sodium iodide symporter', Journal of Endocrinology, vol. 200, n.º 3, pp. 357-365. https://doi.org/10.1677/JOE-08-0246

Characterization of small-molecule inhibitors of the sodium iodide symporter. / Lindenthal, Sabine; Lecat-Guillet, Nathalie; Ondo-Mendez, Alejandro; Ambroise, Yves; Rousseau, Bernard; Pourcher, Thierry.

En: Journal of Endocrinology, Vol. 200, N.º 3, 24.06.2009, p. 357-365.

Resultado de la investigación: Contribución a RevistaArtículo

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T1 - Characterization of small-molecule inhibitors of the sodium iodide symporter

AU - Lindenthal, Sabine

AU - Lecat-Guillet, Nathalie

AU - Ondo-Mendez, Alejandro

AU - Ambroise, Yves

AU - Rousseau, Bernard

AU - Pourcher, Thierry

PY - 2009/6/24

Y1 - 2009/6/24

N2 - The sodium/iodide symporter (NIS) mediates the active transport of iodide from the bloodstream into thyrocytes. NIS function is strategic for the diagnosis and treatment of various thyroid diseases. In addition, a promising anti-cancer strategy based on targeted NIS gene transfer in non-thyroidal cells is currently developed. However, only little information is available concerning the molecular mechanism of NIS-mediated iodide translocation. Ten small molecules have recently been identified using a high-throughput screening method for their inhibitory effect on iodide uptake of NIS-expressing mammalian cells. In the present study, we analyzed these compounds for their rapid and reversible effects on the iodide-induced current in NIS-expressing Xenopus oocytes. Four molecules almost completely inhibited the iodide-induced current; for three of them the effect was irreversible, for one compound the initial current could be fully re-established after washout. Three molecules showed a rapid inhibitory effect of about 75%, half of which was reversible. Another three compounds inhibited the iodide-induced current from 10 to 50%. Some molecules altered the membrane conductance by themselves, i.e. in the absence of iodide. For one of these molecules the observed effect was also found in water-injected oocytes whereas for some others the iodide-independent effect was associated with NIS expression. The tested molecules show a surprisingly high variability in their possible mode of action, and thus are promising tools for further functional characterization of NIS on a molecular level, and they could be useful for medical applications. © 2009 Society for Endocrinology.

AB - The sodium/iodide symporter (NIS) mediates the active transport of iodide from the bloodstream into thyrocytes. NIS function is strategic for the diagnosis and treatment of various thyroid diseases. In addition, a promising anti-cancer strategy based on targeted NIS gene transfer in non-thyroidal cells is currently developed. However, only little information is available concerning the molecular mechanism of NIS-mediated iodide translocation. Ten small molecules have recently been identified using a high-throughput screening method for their inhibitory effect on iodide uptake of NIS-expressing mammalian cells. In the present study, we analyzed these compounds for their rapid and reversible effects on the iodide-induced current in NIS-expressing Xenopus oocytes. Four molecules almost completely inhibited the iodide-induced current; for three of them the effect was irreversible, for one compound the initial current could be fully re-established after washout. Three molecules showed a rapid inhibitory effect of about 75%, half of which was reversible. Another three compounds inhibited the iodide-induced current from 10 to 50%. Some molecules altered the membrane conductance by themselves, i.e. in the absence of iodide. For one of these molecules the observed effect was also found in water-injected oocytes whereas for some others the iodide-independent effect was associated with NIS expression. The tested molecules show a surprisingly high variability in their possible mode of action, and thus are promising tools for further functional characterization of NIS on a molecular level, and they could be useful for medical applications. © 2009 Society for Endocrinology.

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DO - 10.1677/JOE-08-0246

M3 - Article

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VL - 200

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JO - Journal of Endocrinology

JF - Journal of Endocrinology

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