Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.6.1.3 (ATPase)
 65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The concentration of ouabain binding sites (OBS), a measure of the abundance of sodium/potassium-dependent ATPase (Na/K-ATPase), was measured in cerebral cortex (CC), cerebellum (CBL), brown adipose tissue (BAT), and heart of neonatal rats with congenital hypothyroidism. In euthyroid rats, the concentration of OBS was 50- to 100-fold greater in the nervous tissue than in the nonnervous tissue. Congenital hypothyroidism resulted in a significant reduction in the number of OBS in all four tissues. Although in absolute terms (pmol/mg protein) the reduction was greater in the nervous tissues, in relative terms it was much greater in the nonnervous tissues. The restoration of OBS concentration was much more sensitive to T4 in CC, CBL, and BAT than in heart. In contrast, the response of OBS concentration to T3 in hypothyroid rats was greater in the heart, followed by the BAT and CBL, being minimal in CC. The sensitivity to T4 replacement correlated with the degree of the stimulation of the type II 5'deiodinase (5'D-II) by hypothyroidism, whereas the response to exogenous T3 correlated with the fraction of the tissue T3 that derives from plasma T3 and inversely with the plasma T3 concentration required to saturate 50% of the nuclear receptors as reported in previous studies.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Factors determining the differential tissue response of Na/K-ATPase to thyroid hormone in the neonatal rat. 217 Aug 19

On the basis of rat model of congenital hypothyroidism, the following problems were investigated: (1) The biochemical changes of DNA amount in cerebrum, and increase of DNA concentration & decline of protein/DNA in cerebellum. (2) The mitochondria ATPase activity of the cells in cerebral cortex was significantly diminished in hypothyroidism, suggesting that energy metabolism of brain was affected by thyroid hormone. (3) The serum T4 level of hypothyroid offsprings was markedly decreased with increase of serum TSH concentration, while the serum T3 content showed no change. However, 131I uptake rate of thyroid was elevated with peak ahead of time in hypothyroid rats. (4) All the hypothyroid rats were accompanied with delayed body weight growth and decreased weight of brain and several other organs. (5) After replacement therapy with thyroid all the indices mentioned above were improved.
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PMID:[Influence of congenital hypothyroidism on the developing rat brain and improvement after thyroid replacement therapy]. 253 92

Hypothyroidism was induced in rats by treatment with propylthiouracil through the mother's milk throughout the suckling period followed by surgical thyroidectomy without use of radioiodine. The growth of these animals was considerably retarded and their light-dark discriminative operant learning ability was also significantly decreased. Replacement therapy with thyroxine to maintain its normal serum concentration was effective for continuing normal growth and development of learning ability. Therefore, these hypothyroid rats are a useful model of congenital hypothyroidism. Biochemical studies showed that the inhibition of cerebral Na,K-ATPase and succinic dehydrogenase activities detected in early postnatal life in these hypothyroid rats was transient and that normal activities of these enzymes were later regained in adult rats. However, the activity of 2',3'-cyclic nucleotide 3'-phosphohydrolase and the brain myelin remained low throughout life unless thyroxine was administered. Though a critical correlation between biochemical parameters and learning ability is still uncertain, these results suggest that the formation of myelin in the neonatal period is at least dependent on thyroid hormone and would play an important role in mental development.
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PMID:An appropriate model for congenital hypothyroidism in the rat induced by neonatal treatment with propylthiouracil and surgical thyroidectomy: studies on learning ability and biochemical parameters. 339 29

The recently cloned sodium-iodide symporter (NIS) represents a key molecule for thyroid function by efficiently accumulating iodide from the circulation into the thyrocyte against an electrochemical gradient. This uptake requires energy, is coupled to the action of Na+/K+-ATPase, and stimulated by TSH, the main hormone regulating thyroid-specific functions. NIS mutations are found in congenital hypothyroidism, and potential defects in the NIS gene, its expression, or function of the NIS protein are currently under investigation in various thyroid diseases. Increased NIS expression has been found in autonomous adenoma and Graves' disease, decreased levels of NIS protein and/or mRNA were observed in Hashimoto's disease, cold nodules, most thyroid cancers and cell lines derived therefrom. Autoantibodies directed against NIS have been identified in autoimmune thyroid disease and blocking antibodies isolated from sera of patients with Hashimoto's disease inhibit NIS function in NIS-transfected CHO cells. NIS mRNA expression can be up-regulated by retinoic acid in human thyroid carcinoma cell lines whereas retinoic acid treatment decreases NIS expression and function in differentiated rat thyroid FRTL-5 cells. Apart from thyrocytes, NIS is also expressed in other tissues known to transiently accumulate radioiodide, albeit at much lower levels, requiring RT-PCR for detection of the transcript. Diagnostic and therapeutic implications of the recent cloning of the human NIS gene such as development of NIS-directed drugs, ligands, antibodies, vaccines, gene therapeutic approaches combining NIS targeting and expression together with the long-established, efficient and safe method of radioiodide therapy are discussed both for application to thyroid related diseases and carcinoma, and non-thyroid benign and malignant diseases. Apart from these therapeutic and diagnostic perspectives the availability of the NIS gene will also open new opportunities to develop sensitive and homologous diagnostic test systems to identify factors involved in autoimmune thyroid disease, evolution of goitre, adenoma and thyroid cancer as well as NIS-directed new drugs. Advanced and sophisticated molecular diagnostic approaches (RT-PCR from fine needle aspirations, screening for mutations, analysis of gene defects) are already developed for NIS and will complement or overcome some established procedures in thyroid diagnostics.
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PMID:Implications of the molecular characterization of the sodium-iodide symporter (NIS). 986 44