scholarly journals Cloning of the mouse sodium iodide symporter and its expression in the mammary gland and other tissues

2001 ◽  
Vol 170 (1) ◽  
pp. 185-196 ◽  
Author(s):  
B Perron ◽  
AM Rodriguez ◽  
G Leblanc ◽  
T Pourcher
Keyword(s):  
Mammary Gland ◽  
Mammalian Cells ◽  
Sodium Iodide ◽  
Distribution Analysis ◽  
Sodium Iodide Symporter ◽  
Iodide Uptake ◽  
Reading Frame ◽  
Hormone Synthesis ◽  
Iodide Transport ◽  
Lactating Mammary Gland

Iodide concentration in milk by mammals is a necessary step for thyroid hormone synthesis by the newborn. With the purpose of using the mouse as an animal model to analyse the role of the sodium iodide symporter (NIS) in iodide transport and its regulation in the mammary gland, mouse NIS (mNIS) cDNA was isolated from lactating mice. The cloned sequence shows an open reading frame of 1854 nucleotides encoding a protein of 618 amino acids highly homologous to the rat and human NIS (95% and 81% identity respectively). Expression of mNIS in cultured mammalian cells induced cellular iodide accumulation. This iodide uptake process is sodium dependent and inhibited by thiocyanate and perchlorate. Tissue distribution analysis revealed that mNIS mRNAs are predominantly expressed in thyroid, stomach and in the lactating mammary gland and are present to a lower extent in several other tissues. Our data show for the first time that the level of mNIS mRNA is upregulated in the mammary gland during lactation.

scholarly journals A perspective view of sodium iodide symporter research and its clinical implications

2006 ◽  
Vol 155 (4) ◽  
pp. 495-512 ◽  
Author(s):  
Garcilaso Riesco-Eizaguirre ◽  
Pilar Santisteban
Keyword(s):  
Breast Cancer ◽  
Mammary Gland ◽  
Sodium Iodide ◽  
Sodium Iodide Symporter ◽  
Perspective View ◽  
Therapeutic Implications ◽  
Iodide Transport ◽  
Therapy Strategy ◽  
Lactating Mammary Gland ◽  
Gene Therapy Strategy

The sodium iodide symporter (NIS) is an intrinsic plasma membrane protein that mediates active iodide transport into the thyroid gland and into several extrathyroidal tissues, in particular the lactating mammary gland. Cloning and molecular characterization of the NIS have allowed the investigation of its key role in thyroid physiology as well as its potential pathophysiological and therapeutic implications in benign and malignant thyroid diseases. Similarly, elucidating the mechanisms underlying the regulation of NIS in lactating mammary gland and breast cancer, in which more than 80% of cases express endogenous NIS, may lead to findings that have novel implications for pathophysiology and therapy. Two approaches may, in the future, pave the way to extend the use of radioiodide treatment to nonthyroidal cancer. One is based on the reinduction of endogenous NIS expression in thyroid and breast cancer by targeting the main mechanisms involving tumoral transformation and dedifferentiation. The other is based on the application of NIS as a novel cytoreductive gene therapy strategy. NIS offers the unique advantage that it can be used both as a reporter and as a therapeutic gene, so that it is possible to image, monitor, and treat the tumor with radioiodide, just as in differentiated thyroid cancer. This review summarizes the main recent findings in NIS research that have a direct impact on diagnosis and therapeutic management.

scholarly journals Effect of Iodide on Human Choriogonadotropin, Sodium-Iodide Symporter Expression, and Iodide Uptake in BeWo Choriocarcinoma Cells

2007 ◽  
Vol 92 (10) ◽  
pp. 4046-4051 ◽  
Author(s):  
Huika Li ◽  
Kerry Richard ◽  
Brett McKinnon ◽  
Robin H. Mortimer
Keyword(s):  
Gene Expression ◽  
Protein Expression ◽  
Mrna Expression ◽  
Sodium Iodide ◽  
Sodium Iodide Symporter ◽  
Iodide Uptake ◽  
Hormone Synthesis ◽  
Human Choriogonadotropin ◽  
Fetal Thyroid ◽  
Choriocarcinoma Cells

Abstract Context: Active placental transport of maternal iodide by the thyroidal sodium iodide symporter (NIS) provides an essential substrate for fetal thyroid hormone synthesis. NIS is expressed in trophoblast and is regulated by human choriogonadotropin (hCG). In thyroid, iodide down-regulates expression of several genes including NIS. Placentas of iodine-deficient rats demonstrate up-regulation of NIS mRNA, suggesting a role for iodide in regulating placental NIS. Objectives and Methods: The objectives were to examine effects of iodide on expression of NIS and hCG in BeWo choriocarcinoma cells. Gene expression was studied by quantitative real-time PCR. Effects on NIS protein expression were assessed by Western blotting. Functional activity of NIS was measured by 125I uptake. Expression of hCG protein was assessed by immunoassay of secreted hormone. Results: Iodide inhibited NIS mRNA and membrane protein expression as well as 125I uptake, which were paralleled by decreased βhCG mRNA expression and protein secretion. Iodide had no effects on pendrin expression. Addition of hCG increased NIS mRNA expression. This effect was partially inhibited by addition of iodide. The inhibitory effects of iodide on NIS mRNA expression were abolished by propylthiouracil and dithiothreitol. Conclusions: We conclude that expression of placental NIS is modulated by maternal iodide. This may occur through modulation of hCG effects on NIS and hCG gene expression.

scholarly journals Iodide excess regulates its own efflux: a possible involvement of pendrin

2016 ◽  
Vol 310 (7) ◽  
pp. C576-C582 ◽  
Author(s):  
Jamile Calil-Silveira ◽  
Caroline Serrano-Nascimento ◽  
Peter Andreas Kopp ◽  
Maria Tereza Nunes
Keyword(s):  
Plasma Membrane ◽  
Thyroid Hormone ◽  
Thyroid Hormones ◽  
Sodium Iodide ◽  
Inhibitory Effect ◽  
Membrane Insertion ◽  
Sodium Iodide Symporter ◽  
Iodide Uptake ◽  
Hormone Synthesis ◽  
Rat Thyroid

Adequate iodide supply and metabolism are essential for thyroid hormones synthesis. In thyrocytes, iodide uptake is mediated by the sodium-iodide symporter, but several proteins appear to be involved in iodide efflux. Previous studies demonstrated that pendrin is able to mediate apical efflux of iodide in thyrocytes. Acute iodide excess transiently impairs thyroid hormone synthesis, a phenomenon known as the Wolff-Chaikoff effect. Although the escape from this inhibitory effect is not completely understood, it has been related to the inhibition of sodium-iodide symporter-mediated iodide uptake. However, the effects of iodide excess on iodide efflux have not been characterized. Herein, we investigated the consequences of iodide excess on pendrin abundance, subcellular localization, and iodide efflux in rat thyroid PCCl3 cells. Our results indicate that iodide excess increases pendrin abundance and plasma membrane insertion after 24 h of treatment. Moreover, iodide excess increases pendrin half-life. Finally, iodide exposure also increases iodide efflux from PCCl3 cells. In conclusion, these data suggest that pendrin may have an important role in mediating iodide efflux in thyrocytes, especially under conditions of iodide excess.

scholarly journals Characterization of small-molecule inhibitors of the sodium iodide symporter

2008 ◽  
Vol 200 (3) ◽  
pp. 357-365 ◽  
Author(s):  
Sabine Lindenthal ◽  
Nathalie Lecat-Guillet ◽  
Alejandro Ondo-Mendez ◽  
Yves Ambroise ◽  
Bernard Rousseau ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
Sodium Iodide ◽  
Functional Characterization ◽  
Screening Method ◽  
Inhibitory Effect ◽  
Independent Effect ◽  
Induced Current ◽  
Sodium Iodide Symporter ◽  
Iodide Uptake

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.

scholarly journals A Homozygous Missense Mutation of the Sodium/Iodide Symporter Gene Causing Iodide Transport Defect1

1997 ◽  
Vol 82 (12) ◽  
pp. 3966-3971
Author(s):  
Akira Matsuda ◽  
Shinji Kosugi
Keyword(s):  
Missense Mutation ◽  
Ribonucleic Acid ◽  
Sodium Iodide ◽  
Northern Analysis ◽  
Sodium Iodide Symporter ◽  
Iodide Uptake ◽  
Complementary Dna ◽  
Homozygous Missense Mutation ◽  
Iodide Transport ◽  
Nis Gene

Iodide transport defect is a disorder characterized by an inability of the thyroid to maintain an iodide concentration difference between the plasma and the thyroid. The recent cloning of the sodium/iodide symporter (NIS) gene enabled us to characterize the NIS gene in this disorder. We identified a homozygous missense mutation of A→C at nucleotide +1060 in NIS complementary DNA in a male patient who was born from consanguineous marriage, had a huge goiter, and lacked the ability to accumulate iodide but was essentially euthyroid. The mutation results in an amino acid replacement of Thr354→Pro in the middle of the ninth transmembrane domain. COS-7 cells transfected with the mutant NIS complementary DNA showed markedly decreased iodide uptake, confirming that this mutation was the direct cause of the disorder in the patient. Northern analysis of thyroid ribonucleic acid revealed that NIS messenger ribonucleic acid level was markedly increased (>100-fold) compared with that in the normal thyroid, suggesting possible compensation by overexpression.

scholarly journals Histidine residue at position 226 is critical for iodide uptake activity of human sodium/iodide symporter

2008 ◽  
Vol 199 (2) ◽  
pp. 213-219 ◽  
Author(s):  
Shih-Lu Wu ◽  
Tin-Yun Ho ◽  
Ji-An Liang ◽  
Chien-Yun Hsiang
Keyword(s):  
Sodium Iodide ◽  
Sodium Iodide Symporter ◽  
Iodide Uptake ◽  
Uptake Kinetic ◽  
Iodide Transport ◽  
Transmembrane Glycoprotein ◽  
Uptake Activity ◽  
Charged Amino Acid Residue ◽  
Novel Exon

The sodium/iodide symporter (SLC5A5; also known as NIS), a transmembrane glycoprotein principally in the thyroid gland, is responsible for the accumulation of iodide necessary for thyroid hormones. Our previous study indicated that a novel exon 6 deletion (residues 233–280) in SLC5A5 loses the iodide uptake activity. Herein we characterized the role of His-226 in iodide transport of SLC5A5. His-226, a highly conserved extracellular residue among SLC5A5 homologs, was replaced with alanine, aspartic acid, glutamic acid, or lysine. All the SLC5A5 mutants were expressed normally in the cells and targeted correctly to the plasma membrane. However, all of the mutants displayed severe defects in iodide uptake, suggesting that His-226 was critical for iodide uptake. Kinetic analysis further showed that mutation at His-226 led to a dramatic decrease in Vmax. These findings suggested that the decreased levels of iodide uptake activity of SLC5A5 mutants resulted from lower catalytic rates. In conclusion, our data first identified the involvement of extracellular charged amino acid residue in the iodide uptake ability of SLC5A5.

Identification of novel sodium iodide symporter (NIS) interactors which modulate iodide uptake

2016 ◽  
Author(s):  
Alice Fletcher ◽  
Vikki Poole ◽  
Bhavika Modasia ◽  
Waraporn Imruetaicharoenchoke ◽  
Rebecca Thompson ◽  
...  
Keyword(s):  
Sodium Iodide ◽  
Sodium Iodide Symporter ◽  
Iodide Uptake

Identification of novel sodium iodide symporter interactors which modulate iodide uptake

2017 ◽  
Author(s):  
Alice Fletcher ◽  
Vikki Poole ◽  
Bhavika Modasia ◽  
Waraporn Imruetaicharoenchoke ◽  
Rebecca Thompson ◽  
...  
Keyword(s):  
Sodium Iodide ◽  
Sodium Iodide Symporter ◽  
Iodide Uptake

scholarly journals Rapid regulation of thyroid sodium–iodide symporter activity by thyrotrophin and iodine

2005 ◽  
Vol 184 (1) ◽  
pp. 69-76 ◽  
Author(s):  
Andrea C F Ferreira ◽  
Lívia P Lima ◽  
Renata L Araújo ◽  
Glaucia Müller ◽  
Renata P Rocha ◽  
...  
Keyword(s):  
Sodium Iodide ◽  
Iodine Content ◽  
Concomitant Administration ◽  
High Serum ◽  
Sodium Iodide Symporter ◽  
Physiological Control ◽  
Iodide Uptake ◽  
Thyroid Hormone Biosynthesis ◽  
Serum Tsh

Transport of iodide into thyrocytes, a fundamental step in thyroid hormone biosynthesis, depends on the presence of the sodium–iodide symporter (NIS). The importance of the NIS for diagnosis and treatment of diseases has raised several questions about its physiological control. The goal of this study was to evaluate the influence of thyroid iodine content on NIS regulation by thyrotrophin (TSH) in vivo. We showed that 15-min thyroid radioiodine uptake can be a reliable measurement of NIS activity in vivo. The effect of TSH on the NIS was evaluated in rats treated with 1-methyl-2-mercaptoimidazole (MMI; hypothyroid with high serum TSH concentrations) for 21 days, and after 1 (R1d), 2 (R2d), or 5 (R5d) days of withdrawal of MMI. NIS activity was significantly greater in both MMI and R1d rats. In R2d and R5d groups, thyroid iodide uptake returned to normal values, despite continuing high serum TSH, possibly as a result of the re-establishment of iodine organification after withdrawal of MMI. Excess iodine (0.05% NaI for 6 days) promoted a significant reduction in thyroid radioiodide uptake, an effect that was blocked by concomitant administration of MMI, confirming previous findings that iodine organification is essential for the iodide transport blockade seen during iodine overload. Therefore, our data show that modulation of the thyroid NIS by TSH depends primarily on thyroid iodine content and, further, that the regulation of NIS activity is rapid.

Changes of Sodium Iodide Symporter Regulated by IGF-I and TGF-β1 in Mammary Gland Cells from Lactating Mice at Different Iodine Levels

2011 ◽  
Vol 146 (1) ◽  
pp. 73-78 ◽  
Author(s):  
Xue Yu ◽  
Hongmei Shen ◽  
Lixiang Liu ◽  
Lin Lin ◽  
Meili Gao ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Sodium Iodide ◽  
Sodium Iodide Symporter ◽  
Gland Cells ◽  
Igf I ◽  
Mammary Gland Cells ◽  
Tgf Β1
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