Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.27.1 (RNase)
 16,360 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The ability of thyroid hormone to regulate the postnatal changes of the Ca2+-independent transient outward K+ current (It) was studied in rat ventricular myocytes. 2. In rat ventricle, It is very small at birth and then increases markedly between postnatal days 8 and 20. The time course of this increase in current density is similar to that of a significant rise in plasma thyroid hormone (T3) levels. 3. During early development, the density of expression of It can be altered by changes in thyroid hormone levels. Eight days after birth the density of It measured at +50 mV in control animals is 2.2 +/- 0.4 pA pF(-1). This value is about 3-fold larger (6.5 +/- 0.8 pA pF(-1)) in myocytes from age-matched hyperthyroid animals. When the plasma T3 level in newborn rats is not allowed to increase, or is decreased by making animals hypothyroid, this age-dependent increase in It fails to occur. 4. Using RNase protection assays, Kv4.2 and Kv4.3 mRNA levels were measured in ventricular tissues obtained from age-matched 8-day-old control and hyperthyroid rats. In hyperthyroid animals, where an approximately 3-fold increase in It was identified, increases in the mRNA levels for Kv4.2 and Kv4.3 were 1.6-fold and 2.6-fold, respectively. 5. These results show that thyroid hormone can regulate the development of It in rat ventricle. Direct measurements of It density and mRNA levels as a function of development and thyroid hormone levels also strongly suggest that the Kv4.2 and Kv4.3 channels are essential components of It in rat ventricular cells.
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PMID:Thyroid hormone regulates postnatal expression of transient K+ channel isoforms in rat ventricle. 909 33

Pre-translational regulation of subunit c has been suggested to control the biosynthesis of mitochondrial ATP synthase (ATPase) in brown adipose tissue (BAT). Subunit c is encoded by the genes P1 and P2, which encode identical mature proteins. We have determined here the levels of P1 and P2 mRNAs in different tissues, in response to cold acclimation in rats, during ontogenic development of BAT in hamsters, and following thyroid hormone treatment in rat BAT and liver. Quantitative ribonuclease protection analysis showed that both the P1 and P2 mRNAs were present in all rat tissues measured. Their total amount in each tissue corresponded well with the ATPase content of that tissue. While the P1/P2 mRNA ratio is high in ATPase-rich tissues, the P2 mRNA dominates in tissues with less ATPase. Cold acclimation affects P1 but not P2 gene expression in rat BAT. A rapid and transient increase in P1 mRNA is followed by sustained depression, which is accompanied by a decrease in ATPase content. Similarly, ontogenic suppression of ATPase content in hamster BAT was accompanied by suppression of the P1 mRNA levels, while P2 expression was virtually unchanged. Furthermore, when hypothyroid rats were treated with thyroid hormone, the steady-state level of P1 but not of P2 mRNA was significantly increased in liver. BAT was unaffected. We conclude that the P1 and P2 genes for subunit c are differentially regulated in vivo. While the P2 gene is expressed constitutively, the P1 gene responds to different physiological stimuli as a means of modulating the relative content of ATP synthase.
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PMID:ATP synthase subunit c expression: physiological regulation of the P1 and P2 genes. 916 27

The importance of thyroid hormone from embryonic through neonatal life has been documented in both avian and mammalian species. However, the regulation of thyroid hormone production during this period is not completely understood. The objective of this study was to characterize expression of chicken TSHbeta messenger RNA (mRNA) compared with that of thyroid hormones and GH in embryonic and neonatal chickens. Total pituitary RNA was extracted on embryonic days (e-) 11, 13, 15, 17, and 19 and neonatal days (d-) 1, 3, 6, 9, and 12 and subjected to ribonuclease protection assays (RPA) for chicken TSHbeta mRNA. TSHbeta mRNA levels increased through e-19, with e-19 levels being greater than those at all other embryonic ages (P < 0.05). Levels decreased markedly on d-1, then slowly increased to d-6 and stayed elevated through d-12. RIAs were performed for T4, T3, and GH at the same ages. Serum T4 levels increased slowly from less than 1.0 ng/ml on e-11 to a peak of 6.6 ng/ml on d-1 (P < 0.05). After the peak on d-1, posthatch T4 levels stabilized between 3.5-4.5 ng/ml through d-12 (P < 0.05). T3 concentrations were less than 0.25 ng/ml on e-11, increased dramatically between e-19 and d-1 (P < 0.05), and remained high throughout the rest of the experiment, with a concentration of 3.25 ng/ml on d-6 (P < 0.05). GH levels for e-11 through e-17 were below the sensitivity of the GH RIA. On e-19, the GH level was 3 ng/ml and continued to increase through d-12 to a level of 130 ng/ml. As thyroid hormone levels were preceded by maximal TSHbeta mRNA levels on e-19, we next determined whether TSHbeta gene expression on e-19 was under TRH and T3 regulation. E-19 anterior pituitary cells were cultured in serum-free medium with either TRH (10[-8]) or T3 (10[-8]) for 20-24 h. Treatment with T3 significantly decreased levels of TSHbeta mRNA (P < 0.05). However, TRH did not produce a significant increase in TSHbeta mRNA, although TRH did increase TSHbeta mRNA by 60%, on the average, in this study. Therefore, these results indicate that an increase in pituitary TSH production probably regulates thyroid hormone levels during late embryonic development and that negative feedback inhibition of TSH production by thyroid hormones also exists at this critical developmental stage.
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PMID:Expression of chicken thyroid-stimulating hormone beta-subunit messenger ribonucleic acid during embryonic and neonatal development. 944 13

The thyroid hormone receptors (TR) and the retinoic acid receptors share a high degree of homology and their signaling pathways interplay. Thyroid hormone (T3) is known to be associated with various pathological heart conditions. Retinoids are known to ameliorate symptoms in hyperthyroid patients. The aim of this study was to investigate if retinoic acid (RA) can have any effects on TR in cardiac cells and thus play a role in heart disease. Confluent AT-1 cardiomyocytes were treated with RA, T3 depleted medium and DITPA (a cardiotonic T3 analogue) for 48 hours. Solution hybridization for the determination of mRNA for TR alpha 1, alpha 1, beta 1 and beta 2 was performed. RA, T3 and DITPA significantly downregulated the alpha 1, beta 1 and beta 2. The T3 depleted medium did not affect the TR subtypes. The specificity of the solution hybridization method was tested by an RNase protection assay. In conclusion, RA downregulates TR in a similar way as T3 in cardiac cells, indicating a role for RA in thyroid associated heart disease.
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PMID:Downregulation of thyroid hormone receptor subtype mRNA levels by retinoic acid in cultured cardiomyocytes. 946 61

Effects of thyroid hormones on cardiac function or rhythm have been known; however, the mechanism is still unclear. In the present study examined were effects of triiodethyronine (T3) on voltage-gated potassium channel gene expression in rat heart since the potassium channels were presumed to modulate cardiac functions. The mRNA expression of five voltage-gated potassium channel gene alpha subunits (Kv1.2, Kv1.4, Kv1.5, Kv2.1, and Kv4.2) in heart was examined by ribonuclease protection assay in rats which were treated with T3 or propylthyouracil (PTU). All these genes except Kv1.4 mRNA were apparently expressed in the normal rat heart ventricle. Kv1.2 mRNA expression in ventricle was markedly suppressed by T3-treatment and enhanced by PTU-treatment. Interestingly, upregulation of Kv1.4 mRNA expression and downregulation of Kv1.5 mRNA expression were concomitantly induced in the ventricle by the PTU-treatment. In addition, the downregulation of the ventricular Kv1.5 mRNA expression induced by PTU was restored by T3 replacement. No changes of Kv2.1 and Kv4.2 mRNA expression were observed in the ventricles by the T3- or PTU-treatment. In heart atrium the same findings were observed. Kv1.4 mRNA expression, which was detectable in control rat atrium, also decreased significantly by T3-treatment. In contrast, no changes of Kv1.2, Kv1.4, and Kv1.5 mRNA expression in rat brains were induced by T3-treatment. These findings suggest that thyroid hormone specifically influences mRNA expression of Shaker-related potassium channel genes in rat hearts through a common T3 receptor-mediated regulation at a transcriptional level.
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PMID:Thyroid hormone regulates expression of shaker-related potassium channel mRNA in rat heart. 953 13

Deficiency of thyroid hormone (TH) during the perinatal period results in severe neurological abnormalities in rodent cerebellar development. However, the molecular mechanisms of TH action in the developing cerebellum are not fully understood. Of note, a mutant mouse, staggerer, in which the orphan nuclear hormone receptor ROR alpha gene is disrupted, exhibits cerebellar abnormalities similar to those seen in the hypothyroid animals, despite normal thyroid function. We, therefore, speculated that TH (tetraiodo-L-thyronine; T4) may regulate ROR alpha gene expression, which then may regulate genes essential for normal brain development. To test this hypothesis, we studied the changes in ROR alpha gene expression in perinatal hypothyroid rat cerebellum and the effect of TH replacement using Northern blot analysis, ribonuclease protection assay and in situ hybridization histochemistry. During cerebellar development, an approximately 3-fold increase in the cerebellar content of ROR alpha messenger RNA (mRNA) was seen in both propylthiouracil-treated, and propylthiouracil-treated and T4-replaced animals. However, the increase was accelerated when T4 was injected, although the ROR alpha mRNA content was identical, with or without T4, by 30 days after birth (P30). In contrast, T4 treatment suppressed the TH receptor alpha1 and c-erbA alpha2 mRNA content by P30; retinoic acid X receptor-beta mRNA content was not influenced by thyroid status. A significant hybridization signal for ROR alpha mRNA was seen only over Purkinje cells in the cerebellar cortex by in situ hybridization histochemistry. These results indicate that TH alters the timing of expression of the ROR alpha gene in the Purkinje cells of the cerebellar cortex, which may, in turn, influence Purkinje cell differentiation.
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PMID:ROR alpha gene expression in the perinatal rat cerebellum: ontogeny and thyroid hormone regulation. 956 42

Protein disulfide isomerase (PDI) is an enzyme that participates in the formation of disulfide bonds. It is also known to be the subunits of some enzymes and the membrane-associated thyroid hormone-binding protein. In this study, we measured the quantitative distribution of PDI protein in rat tissues and examined the relationship between protein level and enzyme activity in PDI during fasting and refeeding. Western blotting with specific anti-PDI antiserum detected the PDI protein band of 55 kd. Among several tissues, liver contained the largest amount of PDI protein, followed by kidney and fat, in which one-third to one-fourth of the hepatic PDI protein existed. The PDI protein band was also detected in heart and muscle. Fasting for 3 days decreased PDI protein levels in rat liver by 40%; control levels were recovered after 3 days of refeeding. The same change was observed in kidney. PDI activity, measured by the scrambled ribonuclease method, did not show the parallel alteration to PDI protein level in liver and kidney. Isomerase activity decreased to 50% of control values during fasting, but did not recover by refeeding. Thyroidal status did not affect either PDI protein level or isomerase activity. These findings show that fasting and refeeding affect PDI protein and enzyme activity, and that PDI protein level does not always reflect PDI activity.
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PMID:Alterations in the enzyme activity and protein contents of protein disulfide isomerase in rat tissues during fasting and refeeding. 975 Dec 37

Thyroid hormones influence both bone formation and bone resorption. Clinical data and animal studies provide evidence of skeletal site heterogeneity (hip vs. spine) of bone responses to thyroid hormones. In vitro studies also demonstrate direct effects of thyroid hormones on cells of the osteoblast lineage. Transcriptional regulation by thyroid hormone is mediated by ligand-dependent transcription factors called thyroid hormone receptors (TRs). Two genes, c-ErbAalpha and c-ErbAbeta, generate at least four TR isoforms in the rat: TRalpha(1), c-erbAalpha(2), TRbeta(1), and TRbeta(2). Although functional TRs have been identified in cells of the osteoblast lineage, it is still not known if TR isoform expression in bone differs depending upon which skeletal site is examined. We have used ribonuclease protection assay and Northern blot analysis to simultaneously examine the expression of TR isoform mRNAs in adult rat femoral and vertebral bone. TRalpha(1), c-erbAalpha(2), and TRbeta(1) are expressed in both femur and vertebra whole bone. Bone marrow cells from both skeletal sites were also cultured under conditions whereby the osteoprogenitors differentiated into osteoblasts and formed a mineralized extracellular matrix. TRalpha(1), c-erbAalpha(2), and TRbeta(1) mRNAs are each expressed in both femoral and vertebral osteoblast cultures. The presence of TRalpha(1), c-erbAalpha(2), and beta(1) proteins was confirmed by Western analysis of nuclear protein extracts from femoral and vertebral cell cultures. These results indicate that the three predominant TR isoforms are highly expressed in bone and osteoblasts from femurs and vertebrae. Whether there are distinct mechanisms of thyroid hormone action mediated by TRalpha(1), c-erbAalpha(2), and TRbeta(1) at these separate skeletal sites remain to be shown.
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PMID:Expression of multiple thyroid hormone receptor isoforms in rat femoral and vertebral bone and in bone marrow osteogenic cultures. 1044 Sep 37

To understand the expression and role of thyroid hormone nuclear receptors (TRs) in hepatocarcinogenesis, we characterized the TRs in 16 human hepatocellular carcinoma (HCC) specimens. The full-length cDNAs for the two TR subtypes, alpha1 and beta1, were cloned from several tumors by reverse transcription-polymerase chain reaction. Southern blot analysis indicated that, in addition to the full-length cDNA, truncated TRalpha1 and TRbeta1 cDNAs were present in nine tumors (53%). In addition, point mutations detected by the mismatch RNase cleavage assay in TRalpha1 and TRbeta1 were found in 65% and 76% of the tumors, respectively. The mutations were confirmed by DNA sequencing. Interestingly, most of the TRalpha1 mutations were in amino acid codons 209-228 and 245-256, two hot-spots in HCC patients. However, no hot-spot was detected in TRbeta1. The expression of TRalpha1 and TRbeta1 proteins was determined in the tissue extracts by western blotting. TRbeta1 protein was expressed or elevated in 10 tumors but not in normal livers, whereas the expression of TRalpha1 was variable among tumors. The mutant TR proteins were translated in vitro, and their hormone- and DNA-binding activities were evaluated. Abnormal binding to the thyroid hormone response elements was observed. The proteins' DNA binding activity was either partially impaired or completely lost. The high prevalence of TR mutations found in the tumors of patients with hepatocellular carcinoma suggests that mutant TRs could play an important role in liver carcinogenesis.
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PMID:Expression of mutant thyroid hormone nuclear receptors in human hepatocellular carcinoma cells. 1048 22

High affinity-low capacity nuclear triiodothyronine (T3) receptors (TRs), identified as a product of c-erbAalpha proto-oncogene, are expressed in prepubertal rat Sertoli cell. At this age, exogenous T3 treatment as well as hypothyroidism affects Sertoli cell functions. We examined the ontogenetic expression pattern of TRs in the rat testis. Northern analysis confirms that TRs are expressed at high level from fetal development until prepubertal period. RNase protection analysis demonstrates that TRalpha2, the variant isoform of TRalpha1, is constitutively expressed at all ages, while TRalpha3 is absent in the adult gonad. While TRalpha1 and TRalpha2 expression declines during development, Rev-erbAalpha (Rev), the antisense mRNA encoded by the same c-erbAalpha genomic locus, increases beginning 5 days after birth and maximizing in adulthood. TRalpha1, TRalpha2, and Rev mRNAs do not appear to be directly regulated by thyroid hormone in testis; however, short-term neonatal hypothyroidism leads to the expression of TRalpha1 and its variant in adult testis, which is absent in control coeval animals. Thus, during development of rat testis, the levels of messages of genes encoded in the c-erbAalpha. genomic locus have different ontogenetic control. The ontogenetic profile of TRalpha1 and its variant isoforms within the seminiferous epithelium suggests that these receptors are involved in the differentiation of the male gonad.
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PMID:Ontogeny and regulation of variant thyroid hormone receptor isoforms in developing rat testis. 1071 Feb 71


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