Human sodium iodide symporter

Cellular Iodine Transport Body Distribution of the Human Sodium Iodide Symporter... 

Figure 101.1 The human sodium iodide symporter (NIS). A sohematio of the protein structure of the human NIS protein.

Moon DH, Lee SJ, Park KY, Park KK, Ahn SH, Pai MS, Chang H, Lee HK, Ahn IM. Correlation between Tc-pertechnetate uptakes and expressions of human sodium iodide symporter gene in breast tumor tissues. Nucl Med Biol 2001 28 829-834. 

Breous E, Wenzel A, Loos U (2005) The promoter of the human sodium/iodide symporter responds to certain phthalate plasticisers. Mol Cell Endocrinol 244(l-2) 75-78 Calafat AM, Ye X, Silva MJ et al (2006) Human exposure assessment to environmental chemicals using biomonitoring. Int J Androl 29(1) 166-171 (discussion I8I-I65)... 

Breast milk During lactation human mammary tissue expresses the sodium iodide symporter [260], and thus significant transfer of perchlorate into human milk is likely. The presence of micrograms per liter concentrations of perchlorate in milk collected fi om US women [233] confirms lactation as a relevant perchlorate excretion path. If lactating women are secreting perchlorate in milk, then urine-based estimates of total perchlorate exposure for these individuals are likely to be lower than actual [242]. 

Perchloric acid s corrosive properties and ability to cause tissue oxidation are mechanisms of toxicity. Perchlorate (CIOT) disrupts endocrine homeostasis by competitively inhibiting the transport of iodide (I ) into the thyroid through the sodium iodide symporter. Potential human health risks exist from chronic exposure to perchlorate via drinking water. Such risks may include hypothyroidism, goiter, and mental retardation (if exposure occurs during critical periods in neurodevelopment). 

Kogai T, Sajid-Crockett S, Newmarch LS, Liu YY, Brent GA (2008) Phosphoinositide-3-kinase inhibition induces sodium/iodide symporter expression in rat thyroid cells and human papillary thyroid cancer cells. J Endocrinol 199(2) 243-252... 

Table 21.2 Major sites of sodium iodide symporter expression and iodide uptake in the human body...

In the thyroid gland iodide is actively transported into the thyrocyte by the sodium iodide symporter (NIS). The transport of iodide against a gradient is powered by Na /K -ATPase, and competitively inhibited by perchlorate (see review by Carrasco, 1993). With the revelation of the complementary deoxyribonucleic acid (cDNA)-sequence of rat-NIS (Dai et ai, 1996), soon followed by the sequencing of human NIS (Smanik cT gastric wall and the cDNA-sequence of human gastric NIS was revealed (Spitzweg et ai, 1998). 

Figure 32.3 Inhibitory effects of iodide on human thyrocytes function, r, iodide NiS, sodium iodide symporter DUOX, duai oxidase TPO, thyroperoxidase TG, thyroglobulin TGI, iodinated thyroglobuiin X, the substrate converted into the active inhibitory iodinated molecule XI micro, micropinocytosis macro, macropinocytosis prolif, proliferation G.I., gene induction R, receptor Gs, stimulatory G protein of adenylyl cyclase AC, adenylyl cyclase cAMP, cyclic 3 -5 adenosine monophosphate PGE, prostaglandin E1 NE, norepinephrine Gq, stimulatory G protein of phospholipase C DAG, diacylglycerol IPS, inositol 1,4,5-trisphosphate Aa, amino acid ...

Dr Keisuke Iwamoto used genetically-modified human breast adenocarcinoma cell line (MCF-7) cells to overexpress sodium iodide symporter (NIS) and/or LPO, to test the hypothesis that the survival advantage conferred by iodide to human breast cancer cells requires the suppression of LPO, i.e., iodide, but not oxidized iodide (I2) (Iwamoto and Kim, 2005). The model used ionizing radiation (IR)... 

Figure 101.6 The sodium iodide symporter (NIS) and its role in breast oanoer. The oonoept of the NIS and its diagnostic and therapeutic role in breast oanoer. Pharmacologioal stimulation of endogenous NIS expression in breast oanoer by retinoic acid and dexameth-asone allows the applioation of NIS-mediated radionuclides for diagnostio imaging, as well as tumor therapy in breast cancer, as shown by human and mouse studies. Wapnir etal., (2004) Willhauck etai, (2007o).

Iodine plays a key structural role in the thyroid hormones of humans and other mammals, primarily in the form of T3 (triiodothyronine) and T4 (thyroxine). In such samples precursor forms such as MIT (monoiodotyrosine) and DIT (diiodotyrosine) or isomer forms such as rT3 (reverse triiodothyronine) may also be measured. Iodine accounts for 65% of the molecular weight of T4 and 59% of the T3.15-20 mg of iodine is concentrated in the thyroid and hormones with 70% distributed in other tissues. In the cells of these tissues, iodide enters via the sodium-iodide symporter (NIS). 

Reporter genes can also encode for extracellular receptors such as dopamine D2 (200) and SST type-2 receptors (201), or membrane transporters such as the sodium/iodide symporter (202). These human genes have been suggested as candidate reporter genes because they exhibit limited expression in the body. At the same time, radiolabeled tracers with high affinity for these extracellular gene-products have been extensively studied and are approved for human use [e.g., [ F]fluoroethylspiperone for D2 receptors (203), " in-pentetreotide for SST receptors (121), and 123/124/I3ij... 

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