Disease relevance of Tpo

• The observed decrease in TPO mRNA may contribute to the iodine-induced hypothyroidism that is common in patients with Hashimoto's thyroiditis [1].
• Lymphocytic thyroiditis was induced in BB/Wor rats by iodide administration, and thyroidal Tg and TPO mRNA levels were assessed by Northern blot analysis and in situ hybridization, and TNFalpha expression by Northern blot analysis and immunohistochemistry [2].
• CNS hypomyelination in rat terrier dogs with congenital goiter and a mutation in the thyroid peroxidase gene [3].
• These data suggest that insulin deficiency first reduces in vivo TPO activity during short-term experimental diabetes mellitus [4].
• These observations show that in foetal rats, TPO activity increases disproportionately to the thyroid weight, but not in newborn and adult rats, and suggest that preferential synthesis of this enzyme occurs in addition to cell hypertrophy during foetal life [5].

High impact information on Tpo

• Treatment of FRTL-5 thyrocytes with physiological concentrations of thyroid-stimulating hormone (TSH) has been shown to induce increased expressed of thyroglobulin and thyroid peroxidase but to simultaneously decrease expression of the TSH receptor [6].
• We conclude, therefore, that the FRTL-5-specific expression of two thyroid restricted genes, encoding TPO and Tg, relies on a combination of the same trans-acting factors present in thyroid cells [7].
• Mutation of the DNA sequence within any of these regions reduced TPO promoter activity [7].
• In the presence of iodide and hydrogen peroxide, lactoperoxidase, an enzyme model for thyroid peroxidase, catalyzed the conversion of arachidonic acid into several iodinated products [8].
• Three C-glycosylflavones present in millet, glucosylvitexin, glycosylorientin, and vitexin, also inhibited TPO activity [9].

Chemical compound and disease context of Tpo

• A nearly full-length rat thyroid peroxidase cDNA clone was isolated from a bacteriophage cDNA library synthesized using poly A+ RNA isolated from the thyroids of propylthiouracil-treated rats. cDNA probes derived from this clone were used to study rat thyroid peroxidase mRNA levels in response to the level of serum TSH [10].

Biological context of Tpo

• Complete nucleotide sequence of the cDNA for thyroid peroxidase in FRTL5 rat thyroid cells [11].
• The tendency for activities of warm-sensitive neurons to increase progressively at lower Tpo was seen during CO2 inhalation in both AV and AVD rats [12].
• The influence of TSH on thyroid peroxidase (TPO) gene expression was investigated in FRTL5 rat thyroid cells [13].
• We report here the PHS- and lactoperoxidase-catalyzed binding of [14C]amitrole to protein and tRNA, as well as protein binding by rat and hog thyroid peroxidase [14].
• These results suggest that TSH regulates the level of TPO mRNA in FRTL5 cells, in part via the second messenger cAMP and by a nontranscriptional mechanism [13].

Anatomical context of Tpo

• This localizes thyroid peroxidase largely on the endoplasmic reticulum of the cell [15].
• TSH (1 mU/ml) added to FRTL5 cells cultured in the absence of TSH increased TPO mRNA levels 7- to 9-fold compared to levels in control cells [13].
• These studies indicate that antithyroid drugs are unlikely to prevent cell injury by inhibiting hydroxyl radical generation or by scavenging hydroxyl radicals, but are likely to exert their hepatoprotective anti-inflammatory action by inhibiting neutrophil myeloperoxidase, an enzyme akin to thyroid peroxidase [16].
• With the exception of neurosecretory nerve cells, there was a high degree of coincidence between the localization of insulin and TPO [17].
• The staining for TPO in the epithelial cells of normal rats appeared all over the cytoplasm, especially in the apical region [18].

Associations of Tpo with chemical compounds

• In AVD rats, warm-sensitive neurons were rather inhibited by CO2 at higher Tpo [12].
• Inhibition of iodination in this system may be reversible or irreversible, depending on the relative concentrations of iodide and MMI and on the TPO concentration [19].
• Mechanism of action of thioureylene antithyroid drugs in the rat: possible inactivation of thyroid peroxidase by propylthiouracil [20].
• We previously described an in vitro incubation system for studying the mechanism of inhibition of thyroid peroxidase (TPO)-catalyzed iodination by the antithyroid drug 1-methyl-2-mercaptoimidazole (MMI) [19].
• In previous communications we described an in vitro model system containing highly purified thyroid peroxidase (TPO) for studying the mechanism of inhibition of thyroid hormone biosynthesis by the antithyroid drugs, 6-propylthiouracil (PTU) and 1-methyl-2-mercaptoimidazole (MMI) [21].
• EDCs, most potently BP2, may disturb TH homeostasis by inhibiting or inactivating TPO, effects that are even more pronounced in the absence of iodide [22].

Enzymatic interactions of Tpo

• Sequential reactivity of tyrosyl residues of thyroglobulin upon iodination catalyzed by thyroid peroxidase [23].

Other interactions of Tpo

• Tumor necrosis factor-alpha and interferon-gamma modulate gene expression of type I 5'-deiodinase, thyroid peroxidase, and thyroglobulin in FRTL-5 rat thyroid cells [24].
• It takes several hours to be apparent, is maximal between 24-48 h, and is specific, in that thyroid peroxidase and beta-actin mRNA levels are not increased simultaneously [25].
• In the presence of hydrogen peroxide and chloride, neutrophil myeloperoxidase, an enzyme from the same gene superfamily as thyroid peroxidase, generates hypochlorous acid which inactivates alpha-1-proteinase inhibitor (A1PI) present in serum [16].
• They are compatible with the hypothesis that decreased selenium supply, leading to a decreased GSH-Px in the thyroid, increases hydrogen peroxide steady state level and thus thyroid peroxidase activity and thyroid hormone synthesis [26].
• In the control animals of thyroid peroxidase is localized within the membrane of rough endoplasmic reticulum, perinuclear cisternae, microvilli, lamellar structures of the GOLGI apparatus and dispersed through the cytoplasm small vesicles [27].

Analytical, diagnostic and therapeutic context of Tpo

• Northern blot analysis revealed that during the same time course there was a progressive increase in TNFalpha mRNA levels and a progressive decrease in Tg and TPO mRNA levels in the thyroids [2].
• In situ hybridization histochemistry was performed to determine if the decrease in Tg and TPO mRNA levels was associated with thyroid follicular cells in contact with infiltrating mononuclear cells [2].
• In the present study, the potential antithyroid and goitrogenic effects of coal-water extracts (CWE) were investigated in vivo in rats after chronic and acute oral administration of CWE, and in vitro by a thyroid peroxidase (TPO) enzyme system [28].
• Thiol: Protein-disulfide oxidoreductase (TPO) was localized in the brain of juvenile and adult rats by use of the unlabeled immunoperoxidase technique [29].
• In vivo effect of thyrotropin on intracellular translocation of thyroid peroxidase in rat thyroid cells by an indirect immunofluorescence method [18].

References