A novel role for AMP-kinase in the regulation of the Na+/I−-symporter and iodide uptake in the rat thyroid gland

2011 ◽  
Vol 300 (6) ◽  
pp. C1291-C1297 ◽  
Author(s):  
Bruno M. Andrade ◽  
Renata L. Araujo ◽  
Robert L. S. Perry ◽  
Elaine C. L. Souza ◽  
Juliana M. Cazarin ◽  
...  
Keyword(s):  
Thyroid Gland ◽  
Dependent Manner ◽  
Amp Kinase ◽  
Iodide Uptake ◽  
Concentration Dependent Manner ◽  
Thyroid Cells ◽  
Compound C ◽  
Ampk Phosphorylation ◽  
Mrna Content ◽  
Rat Thyroid

The aim of this study was to investigate the role of AMP-kinase (AMPK) in the regulation of iodide uptake by the thyroid gland. Iodide uptake was assessed in PCCL3 follicular thyroid cells exposed to the AMPK agonist 5-aminoimidazole-4-carboxamide-ribonucleoside (AICAR), and also in rat thyroid glands 24 h after a single intraperitoneal injection of AICAR. In PCCL3 cells, AICAR-induced AMPK and acetyl-CoA carboxylase (ACC) phosphorylation decreased iodide uptake in a concentration-dependent manner, while the AMPK inhibitor compound C prevented this effect. In the thyroid gland of rats injected with AICAR, AMPK and ACC phosphorylation was increased and iodide uptake was reduced by ∼35%. Under conditions of increased AMPK phosphorylation/activation such as TSH deprivation or AICAR treatment, significant reductions in cellular Na+/I−-symporter (NIS) protein (∼41%) and mRNA content (∼65%) were observed. The transcriptional (actinomycin D) and translational (cycloheximide) inhibitors, as well as the AMPK inhibitor compound C prevented AICAR-induced reduction of NIS protein content in PCCL3 cells. The presence of TSH in the culture medium reduced AMPK phosphorylation in PCCL3 cells, while inhibition of protein kinase A (PKA) with H89 prevented this effect. Conversely, the adenylyl cyclase activator forskolin abolished the AMPK phosphorylation response induced by TSH withdrawal in PCCL3 cells. These findings demonstrate that TSH suppresses AMPK phosphorylation/activation in a cAMP-PKA-dependent manner. In summary, we provide novel evidence that AMPK is involved in the physiological regulation of iodide uptake, which is an essential step for the formation of thyroid hormones as well as for the regulation of thyroid function.

The inhibitory effect of iodide on growth of rat thyroid (FRTL-5) cells

1988 ◽  
Vol 119 (1) ◽  
pp. 145-151 ◽  
Author(s):  
Motoyasu Saji ◽  
Osamu Isozaki ◽  
Toshio Tsushima ◽  
Mariko Arai ◽  
Megumi Miyakawa ◽  
...  
Keyword(s):  
Cell Growth ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Camp Production ◽  
Iodide Uptake ◽  
Concentration Dependent Manner ◽  
Thyroid Cells ◽  
Camp Generation ◽  
Rat Thyroid ◽  
Sites Of Action

Abstract. The effect of iodide on growth of rat thyroid cells (FRTL-5) was studied. TSH-stimulated cell growth was inhibited by iodide in a concentration-dependent manner, and an effect of iodide was detected at 10−6 mol/l. KClO4 or 1-methylimidazole-2-thiol blocked the effect of iodide, suggesting that iodide uptake and its organification are required to produce the inhibitory effect of iodide on cell growth. Iodide not only decreased TSH-stimulated cAMP production in FRTL-5 cells but also cell growth induced by cAMP. These observations suggest that iodide inhibits TSH-stimulated growth of the cells by attenuating cAMP production and also by acting on the step(s) distal to cAMP generation. The inhibitory effect of iodide was also seen in growth stimulated by insulin, insulin-like growth factor-I or 12-O-tetradecanoyl phorbol 13-acetate, suggesting multiple sites of action of iodide in the process of growth of FRTL-5 cells.

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

2008 ◽  
Vol 294 (4) ◽  
pp. E802-E806 ◽  
Author(s):  
Neil Tran ◽  
Liza Valentín-Blasini ◽  
Benjamin C. Blount ◽  
Caroline Gibbs McCuistion ◽  
Mike S. Fenton ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Active Transport ◽  
Measurement Techniques ◽  
Thyroid Stimulating Hormone ◽  
Dependent Manner ◽  
Iodide Uptake ◽  
Thyroid Cells ◽  
Rat Thyroid ◽  
Inhibit Cell Proliferation ◽  
Stimulating Hormone

Perchlorate blocks thyroidal iodide transport in a dose-dependent manner. The human sodium/iodide symporter (NIS) has a 30-fold higher affinity for perchlorate than for iodide. However, active transport of perchlorate into thyroid cells has not previously been demonstrated by direct measurement techniques. To demonstrate intracellular perchlorate accumulation, we incubated NIS-expressing FRTL-5 rat thyroid cells in various concentrations of perchlorate, and we used a sensitive ion chromatography tandem mass spectrometry method to measure perchlorate accumulation in the cells. Perchlorate caused a dose-related inhibition of 125-iodide uptake at 1–10 μM. The perchlorate content from cell lysate was analyzed, showing a higher amount of perchlorate in cells that were incubated in medium with higher perchlorate concentration. Thyroid-stimulating hormone increased perchlorate uptake in a dose-related manner, thus supporting the hypothesis that perchlorate is actively transported into thyroid cells. Incubation with nonradiolabeled iodide led to a dose-related reduction of intracellular accumulation of perchlorate. To determine potential toxicity of perchlorate, the cells were incubated in 1 nM to 100 μM perchlorate and cell proliferation was measured. Even the highest concentration of perchlorate (100 μM) did not inhibit cell proliferation after 72 h of incubation. In conclusion, perchlorate is actively transported into thyroid cells and does not inhibit cell proliferation.

scholarly journals Sortilin Is a Putative Postendocytic Receptor of Thyroglobulin

Endocrinology ◽  
2008 ◽  
Vol 150 (1) ◽  
pp. 509-518 ◽  
Author(s):  
Roberta Botta ◽  
Simonetta Lisi ◽  
Aldo Pinchera ◽  
Franco Giorgi ◽  
Claudio Marcocci ◽  
...  
Keyword(s):  
Thyroid Gland ◽  
Protein Trafficking ◽  
Cultured Cells ◽  
Endocytic Pathway ◽  
Dependent Manner ◽  
Binding Assays ◽  
Concentration Dependent Manner ◽  
High Affinity ◽  
Rat Thyroid

The Vps10p family member sortilin is involved in various cell processes, including protein trafficking. Here we found that sortilin is expressed in thyroid epithelial cells (thyrocytes) in a TSH-dependent manner, that the hormone precursor thyroglobulin (Tg) is a high-affinity sortilin ligand, and that binding to sortilin occurs after Tg endocytosis, resulting in Tg recycling. Sortilin was found to be expressed intracellularly in thyrocytes, as observed in mouse, human, and rat thyroid as well as in FRTL-5 cells. Sortilin expression was demonstrated to be TSH dependent, both in FRTL-5 cells and in mice treated with methimazole and perchlorate. Plasmon resonance binding assays showed that Tg binds to sortilin in a concentration-dependent manner and with high affinity, with Kd values that paralleled the hormone content of Tg. In addition, we found that Tg and sortilin interact in vivo and in cultured cells, as observed by immunoprecipitation, in mouse thyroid extracts and in COS-7 cells transiently cotransfected with sortilin and Tg. After incubation of FRTL-5 cells with exogenous, labeled Tg, sortilin and Tg interacted intracellularly, presumably within the endocytic pathway, as observed by immunofluorescence and immunoelectron microscopy, the latter technique showing some degree of Tg recycling. This was confirmed in FRTL-5 cells in which Tg recycling was reduced by silencing of the sortilin gene and in CHO cells transfected with sortilin in which recycling was increased. Our findings provide a novel pathway of Tg trafficking and a novel function of sortilin in the thyroid gland, the functional impact of which remains to be established. Evidence for a novel pathway of thyroglobulin trafficking and for a possible novel function of sortilin in the thyroid gland is discussed.

scholarly journals Regulation of thymosin beta10 expression by TSH and other mitogenic signals in the thyroid gland and in cultured thyrocytes

1999 ◽  
pp. 597-607 ◽  
Author(s):  
G Viglietto ◽  
D Califano ◽  
P Bruni ◽  
G Baldassarre ◽  
MT Vento ◽  
...  
Keyword(s):  
Thyroid Gland ◽  
Actin Polymerization ◽  
Mrna Level ◽  
Thyroid Cell ◽  
Dependent Manner ◽  
Follicular Cells ◽  
Thyroid Cells ◽  
Rat Thyroid

OBJECTIVE: To investigate the expression of thymosin beta10 - a small conserved acidic protein involved in the inhibition of actin polymerization - in human and experimental thyroid goiters as well as the regulation exerted by TSH on thymosin beta10 expression in thyroid follicular cells both in vivo and in vitro. DESIGN: To this aim, we have used 5 bioptic specimens from patients affected by thyroid goiter, a well known experimental model of thyroid goitrogenesis (rat fed with the drug propylthiouracil) and a cultured rat thyroid cell line (PC Cl 3 cells) as a model system. RESULTS: We report that the mRNA expression of thymosin beta10 is markedly enhanced in human goiters compared with normal thyroid. In vivo results showed that the steady-state level of thymosin beta10 mRNA is up-regulated in the thyroid gland of propylthiouracil-fed rats in parallel with follicular cell proliferation: iodide administration to goitrous rats, which induced a marked involution of thyroid hyperplasia, reduced the mRNA level of thymosin beta10. Finally, in vitro studies showed that in cultured rat thyrocytes, the expression of thymosin beta10 mRNA is induced in a time- and dose-dependent manner by the activation of pathways which are mitogenic for thyroid cells (i.e. the protein kinase (PK) A and PKC pathways). CONCLUSION: Taken together, the findings reported here demonstrate that thymosin beta10 expression is regulated by extracellular signals that stimulate growth of thyroid cells both in vitro and in vivo, and suggest a role for this protein in thyroid diseases characterized by proliferation of follicular cells.

CORRELATION OF IODIDE TRANSPORT WITH Na+, K+ -ATPase, HCO−3-ATPase AND CARBONIC ANHYDRASE ACTIVITIES IN DIFFERENT FUNCTIONAL STATES OF THE RAT THYROID GLAND

1982 ◽  
Vol 92 (3) ◽  
pp. 371-379 ◽  
Author(s):  
S.-Y. CHOW ◽  
J. W. KEMP ◽  
D. M. WOODBURY
Keyword(s):  
Thyroid Gland ◽  
Carbonic Anhydrase ◽  
Protein Content ◽  
Chronic Treatment ◽  
Cell Water ◽  
Iodide Uptake ◽  
G Cell ◽  
Functional States ◽  
Rat Thyroid ◽  
Rat Thyroid Gland

The effects of thyrotrophin, hypophysectomy, and chronic treatment with thyroxine and methimazole on radioiodide uptake (thyroid/plasma (T/P) 125I− ratio), protein and DNA contents and activities of Na+,K+ -ATPase, HCO−3-ATPase, and carbonic anhydrase (CA) of rat thyroid gland were evaluated. Thyrotrophin given to intact rats slightly increased thyroid iodide uptake, did not affect protein or DNA content, and slightly inhibited CA activity (units/g cell water). Hypophysectomy markedly decreased T/P 125I− ratio, increased protein content, decreased activity of Na+,K+-ATPase, and slightly increased HCO−3-ATPase (nmol/mg DNA per min) and CA (units/g cell water) activities. Thyro-trophin given to hypophysectomized rats (as compared with untreated hypophysectomized control animals) markedly increased T/P 125I− ratio, slightly decreased protein content and decreased Na+,K+-ATPase and CA activities. Chronic treatment with methimazole increased T/P 125I− ratio, decreased protein content, markedly increased Na+,K+-ATPase and HCO−3-ATPase activities, and decreased CA activity. Chronic treatment with thyroxine, in contrast, decreased T/P 125I− ratio, decreased Na+,K+-ATPase activity, and increased CA activity. There was a significant inverse correlation between T/P 125I− ratio and CA activity in follicular cells for the various induced functional states of the thyroid.

scholarly journals S-Nitrosylation of NF-κB p65 Inhibits TSH-Induced Na+/I− Symporter Expression

Endocrinology ◽  
2015 ◽  
Vol 156 (12) ◽  
pp. 4741-4754 ◽  
Author(s):  
Juan Pablo Nicola ◽  
Victoria Peyret ◽  
Magalí Nazar ◽  
Jorge Miguel Romero ◽  
Ariel Maximiliano Lucero ◽  
...  
Keyword(s):  
Gene Expression ◽  
Nuclear Factor Κb ◽  
Specific Gene ◽  
Dependent Manner ◽  
Nuclear Factor ◽  
Concentration Dependent Manner ◽  
Thyroid Cells ◽  
No Donors ◽  
Thyroid Hormone Biosynthesis ◽  
Nis Gene

Nitric oxide (NO) is a ubiquitous signaling molecule involved in a wide variety of cellular physiological processes. In thyroid cells, NO-synthase III-endogenously produced NO reduces TSH-stimulated thyroid-specific gene expression, suggesting a potential autocrine role of NO in modulating thyroid function. Further studies indicate that NO induces thyroid dedifferentiation, because NO donors repress TSH-stimulated iodide (I−) uptake. Here, we investigated the molecular mechanism underlying the NO-inhibited Na+/I− symporter (NIS)-mediated I− uptake in thyroid cells. We showed that NO donors reduce I− uptake in a concentration-dependent manner, which correlates with decreased NIS protein expression. NO-reduced I− uptake results from transcriptional repression of NIS gene rather than posttranslational modifications reducing functional NIS expression at the plasma membrane. We observed that NO donors repress TSH-induced NIS gene expression by reducing the transcriptional activity of the nuclear factor-κB subunit p65. NO-promoted p65 S-nitrosylation reduces p65-mediated transactivation of the NIS promoter in response to TSH stimulation. Overall, our data are consistent with the notion that NO plays a role as an inhibitory signal to counterbalance TSH-stimulated nuclear factor-κB activation, thus modulating thyroid hormone biosynthesis.

scholarly journals Delayed treatment with fenofibrate protects against high-fat diet-induced kidney injury in mice: the possible role of AMPK autophagy

2017 ◽  
Vol 312 (2) ◽  
pp. F323-F334 ◽  
Author(s):  
Minji Sohn ◽  
Keumji Kim ◽  
Md Jamal Uddin ◽  
Gayoung Lee ◽  
Inah Hwang ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Kidney Injury ◽  
Acid Oxidation ◽  
Peroxisome Proliferator ◽  
Dependent Manner ◽  
High Fat ◽  
Concentration Dependent Manner ◽  
Delayed Treatment ◽  
Compound C

Fenofibrate activates not only peroxisome proliferator-activated receptor-α (PPARα) but also adenosine monophosphate-activated protein kinase (AMPK). AMPK-mediated cellular responses protect kidney from high-fat diet (HFD)-induced injury, and autophagy resulting from AMPK activation has been regarded as a stress-response mechanism. Thus the present study examined the role of AMPK and autophagy in the renotherapeutic effects of fenofibrate. C57BL/6J mice were divided into three groups: normal diet (ND), HFD, and HFD + fenofibrate (HFD + FF). Fenofibrate was administered 4 wk after the initiation of the HFD when renal injury was initiated. Mouse proximal tubule cells (mProx24) were used to clarify the role of AMPK. Feeding mice with HFD for 12 wk induced insulin resistance and kidney injury such as albuminuria, glomerulosclerosis, tubular injury, and inflammation, which were effectively inhibited by fenofibrate. In addition, fenofibrate treatment resulted in the activation of renal AMPK, upregulation of fatty acid oxidation (FAO) enzymes and antioxidants, and induction of autophagy in the HFD mice. In mProx24 cells, fenofibrate activated AMPK in a concentration-dependent manner, upregulated FAO enzymes and antioxidants, and induced autophagy, all of which were inhibited by treatment of compound C, an AMPK inhibitor. Fenofibrate-induced autophagy was also significantly blocked by AMPKα1 siRNA but not by PPARα siRNA. Collectively, these results demonstrate that delayed treatment with fenofibrate has a therapeutic effect on HFD-induced kidney injury, at least in part, through the activation of AMPK and induction of subsequent downstream effectors: autophagy, FAO enzymes, and antioxidants.

scholarly journals Propylthiouracil increases sodium/iodide symporter gene expression and iodide uptake in rat thyroid cells in the absence of TSH

Thyroid ◽  
2012 ◽  
pp. 120521124804007
Author(s):  
Sue Mariko ◽  
Takeshi Akama ◽  
Akira Kawashima ◽  
Hannah Nakamura ◽  
Takeshi Hara ◽  
...  
Keyword(s):  
Gene Expression ◽  
Sodium Iodide ◽  
Sodium Iodide Symporter ◽  
Iodide Uptake ◽  
Thyroid Cells ◽  
Rat Thyroid
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