Differential gene expression analysis of iodide-treated rat thyroid follicular cell line PCCl3

Leoni, S; Galante, Pedro A. F.; Ricarte-Filho, Julio C.; Kimura, Edna Teruko

doi:10.1016/j.ygeno.2007.12.009

Cited by 32 publications

(41 citation statements)

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“…Highest overexpression (5.77-fold) was observed with the Tpo (thyroid peroxidase) gene. This contrasts with findings from previous studies reporting either no effect of iodide treatment on Tpo expression (23,39,40) or even downregulation of its expression (41,42) in thyroid cells or lines. The reasons for this discrepancy are unclear but may be due to the different protocols used.…”

Section: Kolypetri and Carayanniotiscontrasting

confidence: 99%

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Apoptosis of NOD.H2^h4Thyrocytes by Low Concentrations of Iodide is Associated with Impaired Control of Oxidative Stress

Kolypetri

Carayanniotis

2014

Thyroid

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Background: Enhanced iodide intake in NOD.H2 h4 mice accelerates the incidence and severity of spontaneous autoimmune thyroiditis (SAT) via an unknown mechanism. A plausible hypothesis is that iodide-induced apoptosis of thyrocytes can create imbalances in antigenic load and/or disruption of immunoregulatory mechanisms that facilitate activation of autoreactive T cells in cervical lymph nodes draining the thyroid. Methods: We examined whether NOD.H2 h4 thyrocytes, exposed to low NaI concentrations in vitro, are more susceptible to apoptosis compared to thyrocytes from CBA/J mice, which are resistant to iodide-accelerated SAT (ISAT). We also looked, at the transcriptional level, for differential activation of genes involved in apoptosis or oxidative stress pathways that may account for potential differences in iodide-mediated apoptosis between NOD.H2 h4 and CBA/J thyrocytes. Results: We report that NOD.H2 h4 thyrocytes, cultured for 24 h at very low (4-8 lM) concentrations of NaI, exhibit high levels (40-55%) of apoptosis, as assessed microscopically following staining with fluorescent caspase inhibitors. Similar treatment of thyrocytes from CBA/J mice, which are resistant to ISAT, yielded significantly lower (10-20%) apoptotic rates. Expression analysis by real-time polymerase chain reaction using arrays of apoptosis-and oxidative stress-related genes showed that NaI intake upregulates the expression of 22 genes involved in ROS metabolism and/or antioxidant function in CBA/J thyrocytes, whereas only two of these genes were upregulated in NOD.H2 h4 thyrocytes. Among the set of overexpressed genes were those encoding thyroid peroxidase (Tpo; 5.77-fold), glutathione peroxidases (Gpx2, Gpx4, Gpx7; 2.03-3.14-fold), peroxiredoxins (Prdx1, Prdx2, Prdx5; 2.27-2.97-fold), superoxide dismutase 1 (Sod1; 3.57-fold), thioredoxin 1 (Txn1; 2.13-fold), and the uncoupling proteins 2 and 3 (Ucp2, Ucp3; 2.01-2.15-fold).Conclusions: The results demonstrate that an impaired control of oxidative stress mechanisms is associated with the observed high susceptibility of NOD.H2 h4 thyrocytes to NaI-mediated apoptosis, and suggest a contributing factor for the development of ISAT in this strain.

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Section: Kolypetri and Carayanniotiscontrasting

confidence: 99%

“…Interestingly, increased expression of Gpx2, Txn1, but not Gpx4 has been previously reported in the rat PCCL3 thyroid cells after iodide treatment in vitro (40,43). Other identified genes were as follows.…”

Section: Kolypetri and Carayanniotismentioning

confidence: 61%

Apoptosis of NOD.H2^h4Thyrocytes by Low Concentrations of Iodide is Associated with Impaired Control of Oxidative Stress

Kolypetri

Carayanniotis

2014

Thyroid

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“…However, in rats previously treated with MMI, which is known to block TPO activity (15,31,42) and, as a consequence, the production of iodolipids, the effect of NaI excess on NIS mRNA abundance and polyadenylation was preserved, which strengthens our hypothesis that iodide itself is the key element for eliciting the effects reported. This assumption is also reinforced by the studies performed by Leoni et al (24), which showed that PCCl3 cells, under iodide and MMI treatment, presented a reduction of NIS gene expression, indicating that this anion per se is capable of regulating the NIS expression.…”

Section: Discussionmentioning

confidence: 69%

“…It can also be expected that the efficiency of the NIS mRNA translation would be impaired in this condition, as pointed out before (30). Even though these findings point to a posttranscriptional control of NIS mRNA expression by iodide, they do not exclude the possibility that longer periods of iodide exposure could also affect the NIS gene transcription rate, as already described (13,14,24).…”

Section: Discussionmentioning

confidence: 73%

Posttranscriptional regulation of sodium-iodide symporter mRNA expression in the rat thyroid gland by acute iodide administration

Serrano‐Nascimento

Calil-Silveira

Nunes

2010

American Journal of Physiology-Cell Physiology

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Serrano-Nascimento C, Calil-Silveira J, Nunes MT. Posttranscriptional regulation of sodium-iodide symporter mRNA expression in the rat thyroid gland by acute iodide administration. Am J Physiol Cell Physiol 298: C893-C899, 2010. First published January 27, 2010 doi:10.1152/ajpcell.00224.2009Iodide is an important regulator of thyroid activity. Its excess elicits the Wolff-Chaikoff effect, characterized by an acute suppression of thyroid hormone synthesis, which has been ascribed to serum TSH reduction or TGF-␤ increase and production of iodolipids in the thyroid. These alterations take hours/days to occur, contrasting with the promptness of WolffChaikoff effect. We investigated whether acute iodide administration could trigger events that precede those changes, such as reduction of sodium-iodide symporter (NIS) mRNA abundance and adenylation, and if perchlorate treatment could counteract them. Rats subjected or not to methylmercaptoimidazole treatment (0.03%) received NaI (2,000 g/0.5 ml saline) or saline intraperitoneally and were killed 30 min up to 24 h later. Another set of animals was treated with iodide and perchlorate, in equimolar doses. NIS mRNA content was evaluated by Northern blotting and real-time PCR, and NIS mRNA poly(A) tail length by rapid amplification of cDNA ends-poly(A) test (RACE-PAT). We observed that NIS mRNA abundance and poly(A) tail length were significantly reduced in all periods of iodide treatment. Perchlorate reversed these effects, indicating that iodide was the agent that triggered the modifications observed. Since the poly(A) tail length of mRNAs is directly associated with their stability and translation efficiency, we can assume that the rapid decay of NIS mRNA abundance observed was due to a reduction of its stability, a condition in which its translation could be impaired. Our data show for the first time that iodide regulates NIS mRNA expression at posttranscriptional level, providing a new mechanism by which iodide exerts its autoregulatory effect on thyroid.NIS mRNA poly(A) tail; RACE-PAT; perchlorate THERE IS A GROWING body of evidence showing that trace elements, such as iron and selenium, modify the expression of proteins that are involved in their transport and metabolism by posttranscriptionally regulating the expression of the mRNAs that encode them. This posttranscriptional regulation mechanism rapidly changes gene expression patterns and occurs mainly at the transcript polyadenylation level, leading to alterations of the mRNA poly(A) tail length, which has been directly associated to transcript stability and translation efficiency (1-3, 34).Iodine is known to acutely regulate the expression of the sodium-iodide symporter (NIS), a specific protein present in the basement membrane of thyroid cells and that mediates iodide uptake (8). This trace element is essential for thyroid hormone synthesis, although its excess causes a blockade of the thyroid function, which is known as the Wolff-Chaikoff effect (29,49). This effect is rapid and transitory, and the mechanisms ...

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“…evidence that an acute high dose of iodine blocks iodide organification by inhibiting the activity of TPo and reduces the expression of niS at both the mrna and protein levels has been presented (16,21). a previous study shows that methimazole, an inhibitor of TPo activity, blocks iodine organification and abolishes an acute Wolff-Chaikoff effect (15).…”

Section: Discussionmentioning

confidence: 99%

Intracellular iodinated compounds affect sodium iodide symporter expression through TSH-mediated signaling pathways

et al. 2010

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Abstract.The mechanisms by which thyroid stimulating hormone (TSH) regulates the expression and activity of sodium iodide symporter (niS) through caMP-PKa have been partially elucidated by many studies. However, the effects of the TSH-mediated Plc-iP3 signaling pathway on the expression of niS and how intracellular iodinated compounds interfere with these signaling pathways are poorly understood. in this study, we investigated the effects of the TSH-mediated caMP-PKa and Plc-iP3 pathways on the expression of niS in the presence of various intracellular iodinated compounds. The intracellular iodinated compounds were formed by treating cells with different concentrations of iodine with or without methimazole (MMi), an inhibitor of iodine organification, in a pig monolayer thyrocyte in vitro. a high concentration of iodine increased niS expression at the mrna and protein levels; however, this phenomenon was not observed in the presence of MMi. Both the caMP-PKa and Plc-iP3 signaling pathways inhibited the expression of niS at low iodine concentrations; however, in thyrocytes treated with high concentrations of iodine, the effect of caMP-PKa on the expression of niS changed from inhibition to promotion, while the Plc-iP3 pathway continued to inhibit niS expression. These findings indicate that intracellular iodinated compounds affect niS expression through the TSH-mediated caMP-PKa and Plc-iP3 pathways.

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Differential gene expression analysis of iodide-treated rat thyroid follicular cell line PCCl3

Cited by 32 publications

References 42 publications

Apoptosis of NOD.H2^h4Thyrocytes by Low Concentrations of Iodide is Associated with Impaired Control of Oxidative Stress

Apoptosis of NOD.H2^h4Thyrocytes by Low Concentrations of Iodide is Associated with Impaired Control of Oxidative Stress

Posttranscriptional regulation of sodium-iodide symporter mRNA expression in the rat thyroid gland by acute iodide administration

Intracellular iodinated compounds affect sodium iodide symporter expression through TSH-mediated signaling pathways

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Differential gene expression analysis of iodide-treated rat thyroid follicular cell line PCCl3

Cited by 32 publications

References 42 publications

Apoptosis of NOD.H2h4Thyrocytes by Low Concentrations of Iodide is Associated with Impaired Control of Oxidative Stress

Apoptosis of NOD.H2h4Thyrocytes by Low Concentrations of Iodide is Associated with Impaired Control of Oxidative Stress

Posttranscriptional regulation of sodium-iodide symporter mRNA expression in the rat thyroid gland by acute iodide administration

Intracellular iodinated compounds affect sodium iodide symporter expression through TSH-mediated signaling pathways

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Apoptosis of NOD.H2^h4Thyrocytes by Low Concentrations of Iodide is Associated with Impaired Control of Oxidative Stress

Apoptosis of NOD.H2^h4Thyrocytes by Low Concentrations of Iodide is Associated with Impaired Control of Oxidative Stress