Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.30.1 (S1 nuclease)
 3,660 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The expression of mRNAs for two cardiac myosins has been studied in the ventricles of hypo- and hyperthyroid rabbits by using cloned cDNA sequences corresponding to the mRNAs of the alpha- and beta-myosin heavy chains (HCs). The temporal change in relative levels of the alpha and beta HC mRNAs after triiodothyronine (T3) treatment of hypothyroid rabbits was determined by nuclease S1 mapping. In the hypothyroid state, only NC beta-mRNA was expressed in the ventricles. The HC alpha-mRNA was first detectable 4 h after administration of T3 (200 micrograms/kg) to hypothyroid animals. By 12, 24, and 72 h, HC alpha-mRNA represented 20, 50, and 90% of total myosin mRNA. The relationship between the relative mRNA levels and relative synthesis rates of myosin HCs was evaluated in 5- to 6-wk-old normal and thyrotoxic rabbits. Myosin synthesis rates were determined by labeling of protein in vivo with [2H]leucine. The V1 (HC alpha) and V3 (HC beta) isomyosins were separated by immune affinity chromatography and the HCs were isolated electrophoretically. In a normal euthyroid group of animals and in animals 12 and 24 h after administration of 200 micrograms of thyroxine, the relative mRNA levels and relative synthesis rates of the alpha and beta HCs were not significantly different. Our results show that, first, thyroid hormone causes a rapid accumulation of HC alpha-mRNA and loss of HC alpha-mRNA, and second, in normal and thyrotoxic rabbits, the relative synthesis rates of HC alpha and HC beta reflect the relative abundance of their respective mRNAs. These data are consistent with the thyroid hormones regulating synthesis of ventricular myosin at steps that precede translation of its message.
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PMID:Expression of myosin heavy chains during thyroid hormone-induced cardiac growth. 375 76

We have characterized the process by which the growth hormone (GH) gene is stimulated in rat pituitary tumor cells (GC or GH3) by the steroid hormone dexamethasone (Dex) and the thyroid hormone, L-triiodothyronine (T3). A primary transcriptional response is detected within 60 minutes of addition of T3 or Dex + T3 to GH-producing cells (GC or GH3). A fivefold transcriptional stimulation of GH nuclear RNA occurs in cells cultured with serum substitute medium and induced with Dex + T3, while T3 alone induces a modest two- to threefold stimulation. The absence of fetal calf serum from the cell culture medium does not decrease the level of transcriptional activity of the GH gene during hormone stimulation. Twenty-four hours after addition of Dex + T3 the cytoplasmic GH mRNA shows a 50-fold increase, as measured by S1 nuclease analysis. This large accumulation of cytoplasmic GH mRNA in contrast to the relatively small changes in GH gene activity is inconsistent with solely a transcriptional mechanism of hormone induction. We suggest that a change in specific GH mRNA stability also takes place in response to Dex + T3. In contrast to other reports, transcriptional stimulation of the GH gene by Dex is insignificant except in the presence of T3.
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PMID:Regulation of growth hormone messenger RNA synthesis by dexamethasone and triiodothyronine. Transcriptional rate and mRNA stability changes in pituitary tumor cells. 398 36

The expression of mRNAs for two cardiac myosins has been examined in the ventricles of hypo- and hyperthyroid rabbits by means of cloned cDNA sequences corresponding to the mRNAs of the alpha- and beta-myosin heavy chains (HCs). The temporal change in the relative levels of the alpha- and beta-HC mRNAs after 3,5,3'-triiodothyronine (T3) treatment of hypothyroid rabbits was determined by nuclease S1 mapping. In the hypothyroid state, only HC beta-mRNA was expressed in the ventricles. The HC alpha-mRNA was first detectable 4 h after administration of T3 (200 micrograms/kg) to hypothyroid animals. By 12 h, HC alpha-mRNA represented 20% of total myosin mRNA, increasing to 50% by 24 h and to about 90% by 72 h. The relationship between the relative mRNA levels and relative synthesis rates of the myosin HCs was evaluated in 5-6-week-old normal and thyrotoxic rabbits. Myosin synthesis rates were determined by labeling of protein in vivo with [3H]leucine. The V1 (HC alpha) and V3 (HC beta) isomyosins were separated by affinity chromatography with monoclonal antibodies, and the HCs were isolated electrophoretically. In a normal euthyroid group of animals and in animals 12 and 24 h after administration of 200 micrograms of 3,5,3',5'-tetraiodothyronine/kg, the relative mRNA levels and relative synthesis rates of the alpha- and beta-HCs were not significantly different. Our results show that, first, thyroid hormone causes a rapid accumulation of HC alpha-mRNA and loss of HC beta-mRNA and, second, in normal and thyrotoxic rabbits, the relative synthesis rates of HC alpha and HC beta reflect the relative abundance of the alpha- and beta-HC mRNAs.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Regulation of myosin synthesis by thyroid hormone: relative change in the alpha- and beta-myosin heavy chain mRNA levels in rabbit heart. 632 4

We have isolated and characterized a rat gene coding for spot 14 mRNA: a hepatic product induced rapidly by thyroid hormone. This gene is present in a single copy/haploid genome, but encodes two mRNA species differing by 170 nucleotides in length. Through S1 nuclease analyses, the difference was mapped to the 3'-end of the mRNA with one species extending 170 nucleotides beyond the 3'-end of the other mRNA. The putative poly(A) addition signals AUUAAA and AAUAAA are found to precede the sites of polyadenylation in the shorter and longer mRNA, respectively. The mRNA codes for a protein of 150 amino acids with a molecular weight of 17,010. The protein-coding region is located closer to the 5'-end of the mRNA, leaving a relatively long 3'-untranslated region, which contains the only intron of 3,150 base pairs within the gene. At approximately 27 base pairs upstream from the start site of the mRNA, a sequence homologous to the TATA box, TAGAAAT , was found.
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PMID:Characterization of a thyroid hormone-responsive gene from rat. 632 13

We investigated the expression of myosin heavy chain (MHC) isoenzymes in embryonic rat ventricles cultured in the anterior eye chamber of an adult rat. In oculo, these grafts beat and mature in an environment where the hormonal milieu can be manipulated. S1 nuclease protection assays were performed on pooled samples of ventricle grafts and compared to normally growing ventricles. At the time of grafting (embryonic day 12, E-12), 23 +/- 4% of the MHC mRNA was of the alpha isoform. While the proportion of ventricular alpha-MHC mRNA did not increase in utero, embryonic ventricles cultured in oculo showed a rapid increase in the relative amount of alpha-MHC mRNA expression (to 84 +/- 10% by 3 days and 86 +/- 5% by 8 days in oculo). alpha-MHC mRNA expression predominated through 8 weeks of culture in oculo, being 76% at 8 weeks in oculo. Additional experiments were performed to determine whether the rapid conversion to alpha-MHC expression resulted from exposure to adult levels of testosterone or thyroid hormone. Reduction of testosterone exposure to nondetectable levels by host orchiectomy did not affect the rapid conversion to alpha-MHC mRNA expression. Exposure to a hypothyroid milieu (i.e., PTU-treated hosts) decreased but did not prevent the conversion from beta- to alpha-MHC mRNA expression at 8 days in oculo; with 83% of the MHC mRNA being of the alpha isoform in hypothyroid hosts compared to 95% in euthyroid hosts. After 8 weeks of culture in hypothyroid hosts, however, alpha-MHC mRNA expression was undetectable in grafted ventricles. These data suggest that E-12 myocardial grafts respond to the hormonal milieu of an adult rat with rapid conversion from beta- to alpha-MHC mRNA expression and that alpha-MHC expression in early developing heart may show reduced sensitivity to downward modulation by a hypothyroid hormonal milieu.
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PMID:Rapid conversion from beta-MHC to alpha-MHC mRNA expression in embryonic rat ventricle cultured in oculo is not dependent on thyroid hormone or testosterone. 747 87

The activity of the apical membrane Na+/H+ exchanger NHE3 isoform of renal or intestinal epithelial cells is chronically regulated by a wide variety of stimuli, including acidosis, cAMP, glucocorticoids, and thyroid hormone. To understand the molecular mechanisms responsible for long term regulation of this cation transporter, we have isolated and determined the structure of this gene from a rat genomic library. The Nh3 gene spans > 40 kilobases and contains 17 exons that are flanked by typical splice donor and acceptor sequences at the exon-intron boundaries. The transcription initiation site was mapped by S1 nuclease protection analyses of mRNA from rat kidney and intestine. Multiple start sites were clustered between nucleotides -100 and -96 relative to the translation initiation codon. An atypical TATA-box and CCAAT-box are centered 30 and 147 nucleotides, respectively, upstream of the predominant transcription initiation site. Sequence analysis of approximately 1.4 kilobases of the 5'-flanking promoter region also revealed the presence of other putative cis-acting elements recognized by various transcription factors (e.g. AP-1, AP-2, C/EBP, NF-I, OCT-1/OTF-1, PEA3, Sp1, glucocorticoid, and thyroid hormone receptors), some of which may participate in the chronic regulation of this gene. The glucocorticoid responsiveness of the Nhe3 gene was assessed by fusing its 5' regulatory region to the firefly luciferase reporter gene and then by measuring the expression of the chimeric gene in transiently transfected renal epithelial OK and LLC-PK1 cells. Glucocorticoid treatment significantly increased the luciferase activity of the chimeric gene in both cell lines, thereby indicating that glucocorticoid regulation of Nhe3 is mediated primarily by a transcriptional mechanism.
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PMID:Genomic organization and glucocorticoid transcriptional activation of the rat Na+/H+ exchanger Nhe3 gene. 863 55


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