The sodium/iodide symporter (NIS) is primarily responsible for iodide accumulation in the thyroid gland for the synthesis of thyroid hormones; however, it can also transport other lyotropic anions in the thyroid gland and nonthyroid tissues. Some NIS substrates have important physiological or clinical roles, and others are environmental contaminants with health-related consequences. The aim of this study was to assess the utility of a yellow fluorescent protein variant, YFP-H148Q/I152L, as a biosensor to monitor the cellular uptake of NIS substrates, including thiocyanate (SCN(-)), nitrate (NO(3)(-)), chlorate (ClO(3)(-)), perchlorate (ClO(4)(-)), and perrhenate (ReO(4)(-)). The fluorescence of purified YFP-H148Q/I152L was suppressed by anions with an order of potency of ReO(4)(-)>ClO(4)(-)=I(-)=SCN(-)=ClO(3)(-)>NO(3)(-)≫Cl(-). Anions also suppressed the fluorescence of YFP-H148Q/I152L expressed in FRTL-5, a thyroid cell line with high NIS expression. Quantitation of intracellular concentrations revealed differences among anions in the affinity and maximal velocity of NIS-mediated uptake as well as in the rate constant for passive efflux. These results suggest that YFP-H148Q/I152L can serve as an intracellular biosensor of NIS-transported anions and may be useful to study the physiology of endogenous anions as well as the health-related consequences of environmental anions.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.ab.2011.04.017 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Per- and polyfluoroalkyl substances (PFAS) exposure is associated with radioiodine therapy resistance and dedifferentiation of differentiated thyroid cancer.
Environ Pollut
January 2025
State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou 510060, P. R. China; Department of Head and Neck Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China. Electronic address:
Differentiated thyroid cancer (DTC) generally has a favorable prognosis, and radioactive iodine (RAI) therapy is typically used for metastatic DTC that continues to progress and poses life-threatening risks. However, resistance to RAI in metastatic DTC significantly impairs treatment effectiveness. This study aims to identify potential compounds that may influence RAI efficacy.
View Article and Find Full Text PDFFunctional characterization of novel compound heterozygous missense gene variants causing congenital dyshormonogenic hypothyroidism.
Front Endocrinol (Lausanne)
January 2025
Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina.
Introduction: The sodium/iodide symporter (NIS) mediates active iodide accumulation in the thyroid follicular cell. Biallelic loss-of-function variants in the NIS-coding gene cause congenital dyshormonogenic hypothyroidism due to a defect in the accumulation of iodide, which is required for thyroid hormonogenesis.
Objective: We aimed to identify, and if so to functionally characterize, novel pathogenic gene variants in a patient diagnosed with severe congenital dyshormonogenic hypothyroidism characterized by undetectable radioiodide accumulation in a eutopic thyroid gland, as well as in the salivary glands.
Unlabelled: We report here transport of the Epidermal Growth Factor Receptor (EGFR), Insulin Receptor, 7-pass transmembrane receptor Smoothened, and 13-pass Sodium-iodide symporter to extracellular vesicles (EVs) for structural and functional studies. Mass spectrometry confirmed the transported proteins as the most abundant in EV membranes, and the presence of many receptor-interacting proteins demonstrates the utility of EVs for characterizing membrane protein interactomes. Cryo-electron tomography of EGFR-containing EVs reveals that EGFR forms clusters in the presence of EGF with a ∼3 nm gap between the inner membrane and cytoplasmic density.
View Article and Find Full Text PDFComparative evaluation of rat and human in vitro assays for evaluation of thyroid toxicity.
ALTEX
December 2024
KaLy-Cell SAS, Plobsheim, France.
The effects of ten test chemicals towards thyroid sodium-iodide symporter (NIS), thyroid peroxidase (TPO), and deiodinases (DIOs) type I, II, and III were evaluated in in vitro rat and human systems and compared. Test chemicals known to directly affect TH levels in vivo were confirmed to effectively inhibit at least one of the tested in vitro endpoints, without significant disparities between species, and the tested compounds known to not affect thyroid function, were found ineffective. Interestingly, Iodide Transport Blocker 5, a potent non-competitive iodine uptake inhibitor, exhibited effects beyond direct NIS inhibition, by impacting NIS function through ATP depletion, and also inhibited TPO and DIO1/2 enzymes, although to a lesser extent.
View Article and Find Full Text PDFThe toxicological role of Myricetin in the progression of human anaplastic thyroid cancer SW1736 cell line.
Food Chem Toxicol
January 2025
Cellular and Molecular Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address:
Aims And Background: Anaplastic thyroid cancer cells lack the capacity to effectively accumulate iodine and are therefore unresponsive to treatment with radioactive iodine. The main objective of this study was to examine the possible therapeutic effects of Myricetin on the SW1736 ATC cell line. In this study, we assessed the influence of Myricetin on iodide absorption, sodium iodide symporter gene expression, and apoptosis induction.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!