Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:1.11.1.8 (thyroid peroxidase)
3,116 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The site of iodination of protein in the thyroid gland (whether intracellular or intraluminal) was ascertained by autoradiographic studies using iodide-125I. In tissue fixed within about 40 sec after intravenous injection of radioiodide the silver grains of autoradiographs were concentrated over the follicular lumen generally as a ring of grains close to the apical border of the follicular cells. The zone of grains was sharply limited toward the cells. No concentration of silver grains was detected associated with any intracellular organelle. The autoradiographic ring which had a minimum width of about 2 mum was continuous along the apical plasma membrane of the follicle cells but there was a drastic reduction in grain density along the plasma membrane of the distal portion of pseudopods. Tissue was fixed so soon after radioiodide injection that it appeared likely that a negligible fraction of radioiodoprotein, if formed in the cell, could have been transferred to the lumen. The observations strongly indicate that the iodination of thyroglobulin occurs in the follicle lumen, probably at the apical surface of the follicle cells. Since in the TSH-treated animals the distribution of the labeling along the apical plasma membrane agrees well with the reported histochemical distribution of thyroperoxidase in this membrane, it is further concluded that iodination may well be catalyzed by peroxidase in the apical plasma membrane.
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PMID:Site of iodination in the rat thyroid gland deduced from electron microscopic autoradiographs. 120 71

Regulation of thyrotropin (TSH) receptor (TSHr) mRNA accumulation as compared with two other thyroid differentiation markers (thyroglobulin and thyroperoxidase (TPO] has been investigated by Northern blot. In dogs in vivo, chronic stimulation of the thyroid TSHr mRNA although it increased the levels of thyroglobulin and TPO mRNA. In dogs treated with thyroxin, the quiescent thyroids expressed normal levels of TSHr and TPO mRNA but depressed levels of thyroglobulin mRNA. In primary cultures of dog thyrocytes, dedifferentiation of the cells by treatment with epidermal growth factor or 12-O-tetradecanoylphorbol-13-acetate led to decreased TSHr mRNA levels and nearly abolished thyroglobulin and TPO gene expression. However, TSHr mRNA was always present, compatible with the fact that these cells, when treated by TSH, reexpress differentiation. Treatment of the cells with TSH or forskolin transiently increased the TSHr mRNA level after 20 h, an effect inhibited by cycloheximide. This up-regulation was confirmed at the protein level: forskolin-treated cells showed an enhanced cAMP response to TSH and an increased binding of labeled TSH to their membranes. Long term TSH treatment led to a slight down-regulation of TSHr mRNA in dog thyrocytes, but in human thyroid cells no marked down-regulation was observed.
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PMID:In vitro and in vivo regulation of thyrotropin receptor mRNA levels in dog and human thyroid cells. 131 Jun 79

Different processes implied in thyroid hormonogenesis (thyroglobulin, thyroperoxidase and hydrogen peroxide generating system expressions) and their regulation by TSH and iodide have been studied using porcine thyroid cells cultured in porous bottomed chambers. This system allowed to reproduce the functional bipolarity. Cells form a tight and polarized monolayer. Both apical and basolateral poles of epithelial cells were independently accessible and the cell layer separated two compartments which can contain different media. A major polarized secretion of thyroglobulin into the apical compartment was observed; it was increased in the presence of TSH as well as the thyroglobulin synthesis and mRNA level. These TSH effects were the consequence of adenylcyclase stimulation. Active transport of iodide, iodination of thyroglobulin and hormonosynthesis took place only in the presence of TSH. These steps occurred at the apical pole of cells. In the culture chamber system, thyroglobulin was weakly iodinated (6 atoms of iodide per mole of thyroglobulin; in vivo up to 40 atoms per mole) but hormonogenesis efficiency was close to this one observed in vivo (40%). Iodide concentrations higher than 0.5 microM daily added to the basal medium inhibited iodination of thyroglobulin and hormonosynthesis. Some components contained in culture media were inhibitors for iodination when they were present in the apical medium such as vitamins, amino acids and phenol red. The culture system appears to be interesting for pharmacological and toxicological studies.
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PMID:Hormonogenesis in thyroid cells cultured on porous bottom chambers. 144 62

The long-term iodination of thyroglobulin secreted into the apical medium of thyroid cells cultured as monolayers on porous bottom chambers reached 5.87 +/- 1.66 atoms of iodine/mol thyroglobulin after 11 days incubation in the presence of TSH (0.1 mU/ml) and iodide (0.5 microM) in the basal medium. This iodinated thyroglobulin contained thyroid hormones (T3 + T4) which involved 22.7% of the thyroglobulin iodine content. The iodoamino acid content was, in residues per mole, 2.2 +/- 0.35 for monoiodotyrosine, 0.74 +/- 0.04 for diiodotyrosine, 0.23 +/- 0.04 for T4, and 0.098 +/- 0.02 for T3. Kinetic studies showed that a minimal level of iodination (2.05 +/- 0.26 atoms iodine/mol thyroglobulin) was necessary for hormonogenesis. A maximal level of iodination and hormonogenesis was obtained with 0.5 microM iodide added daily to the basal medium. In these conditions, hormonogenesis efficiency reached about 40% (a value close to this one observed in vivo). Above 0.5 microM iodide, both iodination and T4 synthesis were inhibited (28.3% and 73.9%, respectively, for 1 microM iodide). Our culture system makes it possible to demonstrate that this high iodide concentration in the basal medium did not increase apical iodide concentration above 10 microM but decreased apical thyroglobulin concentration. The inhibitory effect of iodide on hormonogenesis cannot be due to a competition with tyrosine residues of thyroglobulin for their binding to thyroperoxidase although it could be related, at least in part, to a decrease in protein synthesis.
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PMID:Thyroid hormone synthesis in thyroglobulin secreted by porcine thyroid cells cultured on porous bottom chambers. Effect of iodide. 144 29

Transformation of the thyroid cell line FRTL-5 results in loss or reduction of differentiation as measured by the expression of thyroglobulin and thyroperoxidase, two proteins whose genes are exclusively expressed in thyroid follicular cells. The biochemical mechanisms leading to this phenomenon were investigated in three cell lines obtained by transformation of FRTL-5 cells with Ki-ras, Ha-ras, and polyomavirus middle-T oncogenes. With the ras oncogenes, transformation leads to undetectable expression of the thyroglobulin and thyroperoxidase genes. However, the mechanisms responsible for the extinction of the differentiated phenotype seem to be different for the two ras oncogenes. In Ki-ras-transformed cells, the mRNA encoding TTF-1, a transcription factor controlling thyroglobulin and thyroperoxidase gene expression, is severely reduced. On the contrary, nearly wild-type levels of TTF-1 mRNA are detected in Ha-ras-transformed cells. Furthermore, overexpression of TTF-1 can activate transcription of the thyroglobulin promoter in Ki-ras-transformed cells, whereas it has no effect on thyroglobulin transcription in the Ha-ras-transformed line. Expression of polyoma middle-T antigen in thyroid cells leads to only a reduction of differentiation and does not severely affect either the activity or the amount of TTF-1. Another thyroid cell-specific transcription factor, TTF-2, is more sensitive to transformation, since it disappears in all three transformed lines, and probably contributes to the reduced expression of the differentiated phenotype.
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PMID:Multiple mechanisms of interference between transformation and differentiation in thyroid cells. 144 6

Antibody Dependent Cell Cytotoxicity (ADCC) appears to be involved in Autoimmune Thyroid Disease (AITD). Homologous system may trigger non-specific reactions which might obscure specific ADCC. Heterologous target cells may be useful for studying ADCC, provided relevant antigen(s) are expressed. We therefore tested the capacity of porcine thyroid cells to elicit ADCC reaction in the presence of sera from various patients with AITD. Porcine thyroid cells were used in a 4-hr chromium release assay in the presence of 1/10 heat inactivated human sera and human peripheral blood lymphocytes at a 30:1 effector-target ratio. There was a significant correlation (r = 0.64; P < 0.01) between ADCC activities tested on human or porcine thyroid cells. Serum or IgG effects on porcine thyroid ADCC were dose-dependent between 1/10 to 1/10,000 dilutions. Non-thyroid cell systems were unaffected by thyroid cytotoxic sera. Porcine thyrocyte susceptibility to ADCC peaked at the fourth day of culture and was enhanced by addition of TSH or TSH and methimazole in the culture medium. Using this heterologous system, we demonstrated ADCC activity in a significant proportion of patients with thyroiditis (14/19), Graves' opthalmopathy (19/44) or of mothers of children with congenital hypothyroidism (14/39) and in the children themselves (15/39). Discrepancies observed in some sera between ADCC activity and antithyroperoxidase antibody suggest that thyroperoxidase is not the only antigen involved in ADCC. These results indicate that porcine thyroid cells appear suitable for ADCC assay in patients with AITD. Also this system should be helpful to characterize the antigen-antibody involved.
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PMID:Assessment of antibody dependent cell cytotoxicity in autoimmune thyroid disease using porcine thyroid cells. 147 29

Platelet activating factor (PAF), a phospholipid mediator, has been found to play a role in immune reactions, as well as in many pathophysiological alterations in certain disorders. To determine whether there might be a potential role of PAF in the development of autoimmune thyroid diseases (AITD) we have measured in vitro production of PAF by cultures of pokeweed mitogen-stimulated peripheral blood mononuclear cells (PBMC) obtained from 13 patients with Hashimoto's thyroiditis (HT) and 22 patients with Graves' disease (GD), as well as 18 normal control subjects. Similarly, the levels of PAF in cultures of PBMC after relevant [human thyroglobulin (Tg) and human thyroperoxidase (TPO)] antigenic stimulation in the same preparations were measured by a RIA kit. The basal values of PAF were significantly higher in the PBMC preparations from HT patients than in other two groups. In HT preparations, but not in controls, Tg antigen significantly increased the production of PAF. In GD preparations the response to Tg antigen was also present, but the release of PAF did not reach the levels in control group of preparations. Significantly lower values of PAF production were found in preparations from hyperthyroid GD when compared to the results of preparations from GD patients who were euthyroid and to the results of normal control preparations. The type of treatment and chronicity of disease may also have played some role in these findings, since those treated with radioactive iodine had lower values than those patients who became euthyroid using only antithyroid drugs.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of human thyroglobulin on the production of platelet activating factor from peripheral blood mononuclear cells from patients with autoimmune thyroid diseases. 147 72

The Pax-8 gene, a member of the murine family of paired box-containing genes (Pax genes), is expressed in adult thyroid and in cultured thyroid cell lines. The Pax-8 protein binds, through its paired domain, to the promoters of thyroglobulin and thyroperoxidase, genes that are exclusively expressed in the thyroid. In both promoters, the binding site of Pax-8 overlaps with that of TTF-1, a homeodomain-containing protein involved in the activation of thyroid-specific transcription. Pax-8 activates transcription from cotransfected thyroperoxidase and thyroglobulin promoters, indicating that it may be involved in the establishment, control, or maintenance of the thyroid-differentiated phenotype. Thus, the promoters of thyroglobulin and thyroperoxidase represent the first identified natural targets for transcriptional activation by a paired domain-containing protein.
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PMID:Pax-8, a paired domain-containing protein, binds to a sequence overlapping the recognition site of a homeodomain and activates transcription from two thyroid-specific promoters. 150 16

The presence of autoantibodies (aAbs) to thyroglobulin (TG) and thyroperoxidase (TPO) in most of the patients with autoimmune thyroid disease is now well documented. Studies of these aAbs suggested that some, termed TGPO aAbs, could interact with both TG and TPO. This hypothesis was investigated using IgG fraction from a pool of 25 patients' sera with high TG and TPO aAb titres. Immunopurification of TG, TPO and TGPO aAbs was carried out by sequential affinity chromatography using a large quantity of highly purified human TG and TPO. TGPO aAbs, obtained absorption-elution of affinity purified TG aAbs onto a TPO column, were found to represent about 20% of the TG reactive aAbs and 0.23% of the total amount of IgG. Purified TGPO aAbs were characterized and compared to specific TG and TPO aAbs. In contrast to TG and TPO aAbs which recognized only their target antigen, TGPO aAbs showed high affinity interactions with both TG and TPO. As compared to TG aAbs, TGPO aAbs displayed similar affinity for native TG and higher affinity for denatured TG. Compared to TPO aAbs, TGPO aAbs showed lower affinity for both native and denatured TPO. TGPO aAbs also differed from specific TG and TPO aAbs with regard to IgG subclass distribution and antigen fine specificities as determined by monoclonal antibody assisted mapping of TG and TPO surface epitopes. Taken together, these data indicate that TGPO aAbs are effectively present in the serum of patients with autoimmune thyroid disease. TGPO aAbs may be considered as a subpopulation of TG aAbs with the unique property to cross-react with TPO. The existence of aAbs cross-reacting with these functionally and antigenically related thyroid molecules could lead to a re-examination of the emergence of thyroid autoimmunity.
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PMID:Immunopurification and characterization of thyroid autoantibodies with dual specificity for thyroglobulin and thyroperoxidase. 157 80

Phenol red, commonly used as a pH indicator in tissue culture media, is known to possess estrogenic properties. We investigated the effect of phenol red on the process of thyroglobulin iodination which occurs only at the apical surface of porcine thyroid cells when cultured in porous bottom chambers. When phenol red was added simultaneously to both compartments (apical and basolateral), separated by the polarized monolayer, thyroglobulin iodination was inhibited by about 86% without any effect on thyroglobulin secretion and apical iodine concentration. When phenol red was added separately to either the apical or basal media, inhibition was 68% and 43%, respectively. A large amount of phenol red which was introduced into the basal medium crossed through the monolayer. Thus, inhibition was dependent upon the concentration of phenol red present in the apical compartment. A maximal inhibition was observed from 30 microM apical concentration. Phenol red acts as a substrate for thyroperoxidase in the iodination reaction.
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PMID:Phenol red: an inhibitor of thyroglobulin iodination in cultured porcine thyroid cells. 166 28


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