Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: KEGG:D02259 (NaI)
 1,823 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In 1948, Wolff and Chaikoff reported that organic binding of iodide in the thyroid was decreased when plasma iodide levels were elevated (acute Wolff-Chaikoff effect), and that adaptation or escape from the acute effect occurred in approximately 2 days, in the presence of continued high plasma iodide concentrations. We later demonstrated that the escape is attributable to a decrease in iodide transport into the thyroid, lowering the intrathyroidal iodine content below a critical inhibitory threshold and allowing organification of iodide to resume. We have now measured the rat thyroid sodium/iodide symporter (NIS) messenger RNA (mRNA) and protein levels, in response to both chronic and acute iodide excess, in an attempt to determine the mechanism responsible for the decreased iodide transport. Rats were given 0.05% NaI in their drinking water for 1 and 6 days in the chronic experiments, and a single 2000-microg dose of NaI i.p. in the acute experiments. Serum was collected for iodine and hormone measurements, and thyroids were frozen for subsequent measurement of NIS, TSH receptor, thyroid peroxidase (TPO), thyroglobulin, and cyclophilin mRNAs (by Northern blotting) as well as NIS protein (by Western blotting). Serum T4 and T3 concentrations were significantly decreased at 1 day in the chronic experiments and returned to normal at 6 days, and were unchanged in the acute experiments. Serum TSH levels were unchanged in both paradigms. Both NIS mRNA and protein were decreased at 1 and 6 days after chronic iodide ingestion. NIS mRNA was decreased at 6 and 24 h after acute iodide administration, whereas NIS protein was decreased only at 24 h. TPO mRNA was decreased at 6 days of chronic iodide ingestion and 24 h after acute iodide administration. There were no iodide-induced changes in TSH receptor and thyroglobulin mRNAs. These data suggest that iodide administration decreases both NIS mRNA and protein expression, by a mechanism that is likely to be, at least in part, transcriptional. Our findings support the hypothesis that the escape from the acute Wolff-Chaikoff effect is caused by a decrease in NIS, with a resultant decreased iodide transport into the thyroid. The observed decrease in TPO mRNA may contribute to the iodine-induced hypothyroidism that is common in patients with Hashimoto's thyroiditis.
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PMID:Escape from the acute Wolff-Chaikoff effect is associated with a decrease in thyroid sodium/iodide symporter messenger ribonucleic acid and protein. 1043 93

The sodium/iodide symporter (NIS) has been recognized as an attractive target for radioiodine-mediated cancer gene therapy. In this study we investigated the role of human NIS for cellular uptake of the high LET alpha-emitter astatine-211 ((211)At) in comparison with radioiodine as a potential radionuclide for future applications. A mammalian NIS expression vector was constructed and used to generate six stable NIS-expressing cancer cell lines (three derived from thyroid carcinoma, two from colon carcinoma, one from glioblastoma). Compared with the respective control cell lines, steady state radionuclide uptake of NIS-expressing cell lines increased up to 350-fold for iodine-123 ((123)I), 340-fold for technetium-99m pertechnetate ((99m)TcO(4)(-)) and 60-fold for (211)At. Cellular (211)At accumulation was found to be dependent on extracellular Na(+) ions and displayed a similar sensitivity towards sodium perchlorate inhibition as radioiodide and (99m)TcO(4)(-) uptake. Heterologous competition with unlabelled NaI decreased NIS-mediated (211)At uptake to levels of NIS-negative control cells. Following uptake both radioiodide and (211)At were rapidly (apparent t(1/2) 3-15 min) released by the cells as determined by wash-out experiments. Data of scintigraphic tumour imaging in a xenograft nude mice model of transplanted NIS-modified thyroid cells indicated that radionuclide uptake in NIS-expressing tumours was up to 70 times ((123)I), 25 times ((99m)TcO(4)(-)) and 10 times ((211)At) higher than in control tumours or normal tissues except stomach (3-5 times) and thyroid gland (5-10 times). Thirty-four percent and 14% of the administered activity of (123)I and (211)At, respectively, was found in NIS tumours by region of interest analysis ( n=2). Compared with cell culture experiments, the effective half-life in vivo was greatly prolonged (6.5 h for (123)I, 5.2 h for (211)At) and preliminary dosimetric calculations indicate high tumour absorbed doses (3.5 Gy/MBq(tumour) for (131)I and 50.3 Gy/MBq(tumour) for (211)At). In conclusion, NIS-expressing tumour cell lines of different origin displayed specific radionuclide uptake in vitro and in vivo. We provide first direct evidence that the high-energy alpha-emitter (211)At is efficiently transported by NIS. Application of (211)At may direct higher radiation doses to experimental tumours than those calculated for (131)I. Thus, (211)At may represent a promising alternative radionuclide for future NIS-based tumour therapy.
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PMID:Establishment of radioactive astatine and iodine uptake in cancer cell lines expressing the human sodium/iodide symporter. 1211 Nov 24

Wolff-Chaikoff effect is characterized by the blockade of thyroid hormone synthesis and secretion due to iodine overload. However, the regulation of monocarboxylate transporter 8 during Wolff-Chaikoff effect and its possible role in the rapid reduction of T4 secretion by the thyroid gland remains unclear. Patients with monocarboxylate transporter 8 gene loss-of-function mutations and monocarboxylate transporter 8 knockout mice were shown to have decreased serum T4 levels, indicating that monocarboxylate transporter 8 could be involved in the secretion of thyroid hormones from the thyroid gland. Herein, we aimed to evaluate the regulation of monocarboxylate transporter 8 during the Wolff-Chaikoff effect and the escape from iodine overload, besides the importance of iodine organification for this regulation. Monocarboxylate transporter 8 mRNA and protein levels significantly decreased after 1 day of NaI administration to rats, together with decreased serum T4; while no alteration was observed in LAT2 expression. Moreover, both monocarboxylate transporter 8 expression and serum T4 was restored after 6 days of NaI. The inhibition of thyroperoxidase activity by methimazole prevented the inhibitory effect of NaI on thyroid monocarboxylate transporter 8 expression, suggesting that an active thyroperoxidase is necessary for MCT8 downregulation by iodine overload, similarly to other thyroid markers, such as sodium iodide symporter. Therefore, we conclude that thyroid monocarboxylate transporter 8 expression is downregulated during iodine overload and that the normalization of its expression parallels the escape phenomenon. These data suggest a possible role for monocarboxylate transporter 8 in the changes of thyroid hormones secretion during the Wolff-Chaikoff effect and escape.
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PMID:MCT8 is Downregulated by Short Time Iodine Overload in the Thyroid Gland of Rats. 2602 58

We investigated factors underlying the varying effects of a high dietary iodide intake on serum T4 levels in a wide spectrum of mouse strains, including thyroiditis-susceptible NOD.H2h4, NOD.H2k, and NOD mice, as well as other strains (BALB/c, C57BL/6, NOD.Lc7, and B10.A4R) not previously investigated. Mice were maintained for up to 8 months on control or iodide-supplemented water (NaI 0.05%). On iodized water, serum T4 was reduced in BALB/c (males and females) in association with colloid goiters but was not significantly changed in mice that developed thyroiditis, namely NOD.H2h4 (males and females) or male NOD.H2k mice. Neither goiters nor decreased T4 developed in C57BL/6, NOD, NOD.Lc7, or B10.A4R female mice. In further studies, we focused on males in the BALB/c and NOD.H2h4 strains that demonstrated a large divergence in the T4 response to excess iodide. Excess iodide ingestion increased serum TSH levels to the same extent in both strains, yet thyroidal sodium iodide symporter (NIS) messenger RNA (mRNA) levels (quantitative polymerase chain reaction) revealed greatly divergent responses. NOD.H2h4 mice that remained euthyroid displayed a physiological NIS iodine autoregulatory response, whereas NIS mRNA was inappropriately elevated in BALB/c mice that became hypothyroid. Thus, autoimmune thyroiditis-prone NOD.H2h4 mice adapted normally to a high iodide intake, presumably by escape from the Wolff-Chaikoff block. In contrast, BALB/c mice that did not spontaneously develop thyroiditis failed to escape from this block and became hypothyroid. These data in mice may provide insight into the mechanism by which iodide-induced hypothyroidism occurs in some humans without an underlying thyroid disorder.
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PMID:Aberrant Iodine Autoregulation Induces Hypothyroidism in a Mouse Strain in the Absence of Thyroid Autoimmunity. 2937 95