Anion Selectivity by the Sodium Iodide Symporter

Sande, Jacqueline Van; Massart, C.; Beauwens, Renaud; Schoutens, André; Costagliola, Sabine; Je, Dumont; Wolff, J.

doi:10.1210/en.2002-220744

Cited by 150 publications

(101 citation statements)

References 20 publications

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“…; P<0.001; n=5). This confirmed the functionality of exogenous NIS in COS-7 cells, as has been demonstrated previously in a number of publications (Castro et al, 1999a;De la Vieja et al, 2004;De la Vieja et al, 2005;Smanik et al, 1996;Smanik et al, 1997;Van Sande et al, 2003;Zhang et al, 2005). Furthermore, the level of uptake was very similar to that demonstrated by Zhang and colleagues (Zhang et al, 2005).…”

Section: Nis Colocalises With Pbfsupporting

confidence: 89%

A novel mechanism of sodium iodide symporter repression in differentiated thyroid cancer

Smith

Read

Turnell

et al. 2009

Journal of Cell Science

143

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Differentiated thyroid cancers and their metastases frequently exhibit reduced iodide uptake, impacting on the efficacy of radioiodine ablation therapy. PTTG binding factor (PBF) is a proto-oncogene implicated in the pathogenesis of thyroid cancer. We recently reported that PBF inhibits iodide uptake, and have now elucidated a mechanism by which PBF directly modulates sodium iodide symporter (NIS) activity in vitro. In subcellular localisation studies, PBF overexpression resulted in the redistribution of NIS from the plasma membrane into intracellular vesicles, where it colocalised with the tetraspanin CD63. Cell-surface biotinylation assays confirmed a reduction in plasma membrane NIS expression following PBF transfection compared with vector-only treatment. Coimmunoprecipitation and GST-pull-down experiments demonstrated a direct interaction between NIS and PBF, the functional consequence of which was assessed using iodide-uptake studies in rat thyroid FRTL-5 cells. PBF repressed iodide uptake, whereas three deletion mutants, which did not localise within intracellular vesicles, lost the ability to inhibit NIS activity. In summary, we present an entirely novel mechanism by which the proto-oncogene PBF binds NIS and alters its subcellular localisation, thereby regulating its ability to uptake iodide. Given that PBF is overexpressed in thyroid cancer, these findings have profound implications for thyroid cancer ablation using radioiodine.

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Section: Nis Colocalises With Pbfsupporting

confidence: 89%

A novel mechanism of sodium iodide symporter repression in differentiated thyroid cancer

Smith

Read

Turnell

et al. 2009

Journal of Cell Science

143

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“…This is the initial step in the biosynthesis of the iodine-containing hormones thyroxine and triiodothyronine, which are essential for growth, development, and many metabolic reactions (22). NIS has also been shown to have a high affinity for many ions of similar size and charge to iodide, such as perchlorate, thiocyanate, nitrate, bromide, perrhenate, and pertechnetate (31,34). Many of these anions, including perchlorate, have been shown to be competitive inhibitors of iodide transport (34).…”

mentioning

confidence: 99%

Thyroid-stimulating hormone increases active transport of perchlorate into thyroid cells

Tran

Valentín-Blasini²,

Blount³

et al. 2008

American Journal of Physiology-Endocrinology and Metabolism

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“…Van Sande et al (2003) -and ClO 4 -resulted in a time-and concentration-dependent decrease in cellular fluorescence. The affinity of perchlorate for uptake was much higher than that of chlorate.…”

Section: Mode Of Actionmentioning

confidence: 92%

Risks for public health related to the presence of chlorate in food

Publication¹

2015

EFS2

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Following a request from the European Commission, the risks to human health related to the presence of chlorate in food were assessed by the EFSA Panel on Contaminants in the Food Chain (CONTAM Panel). The presence of chlorate in food can arise from the use of chlorinated water for food processing and the disinfection of foodprocessing equipment. Inhibition of iodine uptake in humans was identified as the critical effect for chronic exposure to chlorate. A tolerable daily intake (TDI) of 3 µg chlorate/kg body weight (b.w.) was set by readacross from a TDI of 0.3 µg/kg b.w. derived for this effect for perchlorate, multiplied by a factor of 10 to account for the lower potency of chlorate. Formation of methaemoglobin was identified as the critical acute effect of chlorate. An acute reference dose (ARfD) of 36 µg chlorate/kg b.w. was derived from a no-observedeffect-level for chlorate in a controlled clinical study. Chronic exposure of adolescent and adult age classes did not exceed the TDI. However, at the 95th percentile the TDI was exceeded in all surveys in 'Infants' and 'Toddlers' and in some surveys in 'Other children'. Chronic exposures are of concern in particular in younger age groups with mild or moderate iodine deficiency. Mean and 95th percentile acute exposures were below the ARfD for all age groups indicating no concern. Based on the current practices in food industry, application of a hypothetical maximum residue limit (MRL) of 0.7 mg/kg for all foodstuffs and drinking water would only minimally reduce acute/chronic exposures and related risks. Assuming chlorate concentrations of 0.7 mg/kg for all foods and drinking water consumed in a day, acute exposures would increase by up to about 5-fold and the ARfD be exceeded at mean estimates in 'Infants' and 'Toddlers' and at 95th percentile also in 'Other children'and 'Adults'. Chlorate is formed as a by-product when using chlorine, chlorine dioxide or hypochlorite for the disinfection of drinking water, water for food production and surfaces coming into contact with food. Chlorination of animal-derived food is not allowed in the EU, while washing of plant-derived food with chlorine disinfected water can be permitted under national regulations. No maximum levels for chlorate in drinking water have been set in the European Union (EU) while the World Health Organisation (WHO) has established a guideline level for chlorate in drinking water of 0.7 mg/L. © EuropeanIn many fruit and vegetable commodities chlorate levels exceeding the default MRL of 0.01 mg/kg are found.Based on the available information, the CONTAM Panel assumes that chlorate residues in food result mainly from the use of chlorinated water for food processing (e.g. washing) and from the disinfection of surfaces and food processing equipment coming into contact with food.The EFSA Evidence Management Unit (DATA Unit) launched a call for data on chlorate levels in food and drinking water. After a quality assessment of the analytical data and their evaluation, 8 028 samples remained for anal...

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Anion Selectivity by the Sodium Iodide Symporter

Cited by 150 publications

References 20 publications

A novel mechanism of sodium iodide symporter repression in differentiated thyroid cancer

A novel mechanism of sodium iodide symporter repression in differentiated thyroid cancer

Thyroid-stimulating hormone increases active transport of perchlorate into thyroid cells

Risks for public health related to the presence of chlorate in food

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