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:3.1.27.5 (RNase)
17,967 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Regulation of glucocorticoid receptor (GR) expression by its cognate ligand was examined in the glucocorticoid-sensitive human leukemic T-cell line 6TG1.1 and in the human B-cell line IM-9. In contrast to the decrease in GR mRNA seen in IM-9 cells after treatment with 1 microM dexamethasone for 16-18 h, treatment of 6TG1.1 cells resulted in an 8-fold increase in GR mRNA, as determined by Northern blot and RNase protection analysis, with a corresponding 3- to 4-fold increase in GR protein. Half-maximal induction of GR mRNA and protein in 6TG1.1 cells was observed between 10-100 nM dexamethasone, and inclusion of 1 microM RU 38486 completely blocked the effects of 100 nM dexamethasone, demonstrating that positive autoregulation of GR expression in 6TG1.1 cells is a receptor-mediated response. Positive autoregulation of GR expression was also observed in glucocorticoid-resistant CEM-C1 cells, which contain functional GR, but whose growth is unaffected by glucocorticoids. Thus, positive autoregulation is neither a consequence nor the sole cause of growth arrest. The degree of negative autoregulation in IM-9 cells and positive autoregulation in 6TG1.1 cells was unaffected by inhibition of protein synthesis with cycloheximide. Measurement of GR mRNA turnover in 6TG1.1 cells treated with actinomycin-D revealed a half-life of 2.5 h, which was unaffected by dexamethasone treatment. A similar half-life was determined in IM-9 cells and was also unaffected by steroid treatment. These results are consistent with the interpretation that glucocorticoid-mediated autoregulation of GR expression is a tissue-specific primary transcriptional response.
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PMID:Differential autoregulation of glucocorticoid receptor expression in human T- and B-cell lines. 831 74

The establishment of transformation of primary baby rat kidney epithelial cells by human papillomavirus type 16 DNA requires glucocorticoid hormones (Pater et al., Nature (Lond.), 335: 832-835, 1988). In this report we provide evidence that growth of transformed baby rat kidney cells in culture also requires glucocorticoids. However, transformed cells for which growth does not require hormone readily arise after a brief period of crisis, if cultured without added hormone. No reduction of glucocorticoid receptor was evident in non-hormone-requiring cells. The expression of human papillomavirus 16 RNA in these cells was analyzed by Northern blot, primer extension, and RNase protection analysis. Cells that do not require hormone had greatly reduced levels of transcripts initiated from the viral P97 promoter. However, there is evidence for compensating alterations to allow more efficient expression of E7 mRNA, since the growth of these cells is correlated with altered patterns of viral RNA expression and processing.
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PMID:Glucocorticoid requirement for growth of human papillomavirus 16-transformed primary rat kidney epithelial cells: correlation of development of hormone resistance with viral RNA expression and processing. 839 83

Recent studies have shown that corticotropin releasing factor (CRF) stimulates c-fos gene expression in the AtT-20 corticotroph cell line, and that overexpression of c-Fos results in activation of POMC gene transcription. Since transactivation by c-Fos requires dimerization with a Jun family member to form the active transcription factor AP-1, we have examined the expression of multiple fos and jun related genes and have correlated their expression with AP-1 DNA binding activity in AtT-20 nuclear extracts after stimulation with CRF. Although basal expression of c-fos mRNA was extremely low, it was rapidly and transiently stimulated in AtT-20 cells following administration of either constant or a single pulse of CRF. In contrast, basal expression of c-jun mRNA was slightly higher and underwent little or no change in response to CRF. Specific ribonuclease protection analysis showed that in addition to c-fos, mRNA transcripts encoding fos B and jun B were rapidly stimulated in response to CRF, though levels of induced fos B mRNA were 20-40 times lower than c-fos or jun B, respectively. Gel shift analysis demonstrated that CRF caused a sustained increase in AP-1 DNA binding to both a canonical AP-1 element as well as to the POMC exon-1 AP-1 site. Studies with specific antisera directed against c-Fos revealed that although no c-Fos could be detected in AP-1 complexes in basal cell extracts, c-Fos became a prominent component of AP-1 following CRF stimulation, reaching maximal levels by 4 h. Despite the fact that AP-1 DNA binding activity remained elevated for at least 24 h after CRF, c-Fos was most prominent during the early phase of the response. Similarly, JunB was shown to be a major component of AP-1 DNA binding activity in CRF-stimulated AtT-20 nuclear extracts that persisted for at least 24h after stimulation. Despite the obvious induction of fos B mRNA in response to CRF, FosB protein was not detected in DNA bound AP-1 complexes. These data demonstrate that CRF is a potent stimulus for corticotroph expression of c-fos, jun B and fos B, and suggest that the subsequent increase in AP-1 may play a role in activation of gene expression and/or as a modulator of glucocorticoid receptor function.
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PMID:CRF stimulates expression of multiple fos and jun related genes in the AtT-20 corticotroph cell. 879 51

Hormones may produce long-term effects on excitability by regulating K+ channel gene expression. Previous studies demonstrated that administration of dexamethasone, a glucocorticoid receptor agonist, to adrenalectomized rats, rapidly induces Kv1.5 K+ channel expression in the ventricle of the hear. Here, RNase protection assays and Northern blots are used to examine the cell type specificity of dexamethasone action and to test whether Kv1.5 gene expression can be regulated by a physiological stimulus. We show that Kv1.5 mRNA expression in the central nervous system is highest in the hypothalamus. However, dexamethasone treatment of adrenalectomized rats fails to affect Kv1.5 mRNA levels in hypothalamus or lung. In contrast, dramatic upregulation of Kv1.5 mRNA is seen in skeletal muscle and pituitary. Increased Kv1.5 message also found in isolated ventricular cardiomyocytes following in vivo treatment with dexamethasone. Finally, it is shown that cold stress of intact rats significantly increases cardiac Kv1.5 mRNA expression. We conclude that dexamethasone induction of Kv1.5 gene is tissue-specific. Furthermore, our results suggest that stress may act via glucocorticoids to increase Kv1.5 gene expression in ventricular cardiomyocytes. Hence, K+ channel gene expression can be influenced by physiological and pharmacological stimuli.
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PMID:Dexamethasone and stress upregulate Kv1.5 K+ channel gene expression in rat ventricular myocytes. 893 30

Hormones can regulate the expression of their own receptor. We have examined whether adrenalectomy (ADX) and hormone replacement by physiological doses of aldosterone or dexamethasone could modulate the expression of glucocorticoid receptor (GR) or mineralocorticoid receptor (MR) at the mRNA level in the rat kidney, distal colon, and heart. Adult rats were adrenalectomized and received or did not receive an infusion of aldosterone (5 micrograms.100 g-1.day-1) or dexamethasone (10 micrograms.100 g-1.day-1). No significant change in steady-state levels of both MR and GR mRNA was detectable by using ribonuclease (RNase) protection assay (RPA) after either ADX or hormone replacement. Because the kidney is heterogeneous with regard to MR expression, RPA was adapted for measurements on microdissected nephron segments. GR mRNA is expressed at comparable levels all along the nephron, whereas MR mRNA is restricted to the distal nephron. No effect of ADX or GR and MR mRNA levels was detected in any nephron segment that was either aldosterone sensitive or insensitive. In situ hybridization confirmed the absence of corticosteroid-dependent modulation of MR mRNA in all kidney cell types. We conclude that variations of corticosteroid status do not affect MR and GR mRNA steady-state levels in heart, colon, and kidney and thus do not participate to the functional adaptations that are known to depend on hormonal status.
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PMID:Corticosteroid receptor mRNA expression is unaffected by corticosteroids in rat kidney, heart, and colon. 896 34

Genomic sequences flanking the 5' end of the cDNA encoding isoform C beta 2 of the catalytic subunit of bovine cAMP-dependent protein kinase were cloned, sequenced and analyzed for promoter activity and transcription initiation sites. A region of 913 bp upstream the translation initiator ATG was amplified from genomic DNA by vectorette polymerase chain reaction. In primer extension reactions and RNase protection assays, residues C (at position -91), T (-71) and G (-70) were found to serve as transcription initiation sites of the gene. Amplification products and sub-fragments thereof were ligated upstream of the reporter gene chloramphenicol acetyltransferase to test for promoter activity. Constructs were transiently transfected into a Chinese hamster ovary cell line which was shown to express endogenous C beta 2 mRNA. The genomic sequence upstream the C beta 2 cDNA does have promoter activity. The region from position -51 to -292 proved sufficient to drive efficient transcription of the reporter gene. The promoter is AT rich (68%), does not contain a TATA box within 50 bp upstream of the first initiation site and possesses putative binding sites for several transcription factors such as PEA-3 and a glucocorticoid receptor.
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PMID:Promoter of the gene encoding the bovine catalytic subunit of cAMP-dependent protein kinase isoform C beta 2. 898 58

We investigated the effectiveness of lipopolysaccharide (LPS) and muramyl dipeptide (MDP) administered into the brain to induce anorexia in acutely fasted Wistar rats allowed to refeed. We also assayed for changes in mRNA levels of IL-1 system components, TNF-alpha, TGF-beta1, glycoprotein 130 (gp 130), leptin receptor (OB-R), pro-opiomelanocortin (POMC), neuropeptide Y (NPY), glucocorticoid receptor (GR), and CRF receptor (CRF-R) in selected brain regions. The data show that LPS and MDP induced anorexia differentially during refeeding. LPS-induced anorexia was of a stronger magnitude and duration than that of MDP. RNase protection assays showed that LPS and MDP significantly increased the expression of IL-1beta, IL-1 receptor type I, and TNF-alpha mRNAs in the cerebellum, hippocampus, and hypothalamus; LPS was more potent in all cases. MDP treatment, on the other hand, induced a stronger increase in hypothalamic levels of IL-1 receptor antagonist (IL-1Ra) and TGF-beta1 mRNAs relative to LPS. In addition, competitive RT-PCR analysis showed that LPS induced an eleven-fold increase in IL-1alpha mRNA in the hypothalamus relative to vehicle. These findings suggest that LPS and MDP mediate anorexia through different cytokine mechanisms. A stronger up-regulation of anti-inflammatory cytokines (IL-1Ra and TGF-beta1) mRNA expression by MDP may be involved in the weaker MDP-induced anorexia relative to LPS. No significant changes were observed in the peptide components examined except for an up-regulation in cerebellar gp 130 mRNA and down-regulation of hypothalamic GR mRNA expression in response to LPS or MDP. This study shows that LPS and MDP induce anorexia in fasted rats allowed to refeed, and suggests an important role for endogenous cytokine-cytokine interactions.
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PMID:Lipopolysaccharide (LPS)- and muramyl dipeptide (MDP)-induced anorexia during refeeding following acute fasting: characterization of brain cytokine and neuropeptide systems mRNAs. 962 98

A new concept in reproductive endocrinology is that the status of the ovary as a glucocorticoid target organ alters with follicular development. Evidence for a physiological role of glucocorticoids in the regulation of ovarian folliculogenesis has been strengthened by the discovery that 11beta-hydroxysteroid dehydrogenase (11betaHSD) mRNA expression in human granulosa cells is developmentally regulated. In this study, we quantified the pattern of expression and investigated the cellular location of 11betaHSD type 1 (11betaHSD1), 11betaHSD type 2 (11betaHSD2), glucocorticoid receptor (GR), and mineralocorticoid receptor (MR) mRNAs during follicular maturation in rat ovary. Immature female rats received treatment with eCG to induce preovulatory follicular development or eCG followed by hCG to induce luteinization. 11betaHSD1, 11betaHSD2, GR, and MR mRNAs were all detectable by ribonuclease protection assay in ovarian total RNA. Treatment with eCG alone caused an approximately 8-fold increase in the ovarian level of 11betaHSD1 mRNA, which rose to approximately 30-fold after additional treatment with hCG. Equine CG alone did not measurably affect the ovarian 11betaHSD2 mRNA level, but additional treatment with hCG reduced it to 34% of the control level. Expression of GR mRNA was unchanged by any gonadotropin treatment, while MR mRNA was down-regulated. A similar pattern of 11betaHSD1, 11betaHSD2, GR, and MR mRNA expression was observed in isolated granulosa cells. These results provide direct experimental evidence that 11betaHSD genes are gonadotropically regulated in the rat ovary, including granulosa cells, and are consistent with a shift in glucocorticoid metabolism from inactivation (due to oxidation by 11betaHSD2) to activation (reduction by 11betaHSD1) during hCG-induced granulosa cell luteinization.
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PMID:Expression of 11beta-hydroxysteroid dehydrogenase, glucocorticoid receptor, and mineralocorticoid receptor genes in rat ovary. 991 98

A cDNA library from plasma membrane glucocorticoid receptor-enriched (mGR(++)) S- 49 mouse T lymphoma cells was screened with full-length rat intracellular GR (iGR) cDNA, BUGR-2 antibody, and PCR amplimers to portions of the mouse GR cDNA. One or two single-base substitutions resulting in amino acid changes (which do not incapacitate the receptor) were found in all but one clone: Val437 --> Gly (located in the first zinc finger), and Glu546 --> Gly (in the steroid-binding domain). Two previously unidentified exon 1 variants (1D and 1E), and two of three previously reported variants (1A, 1B) were found to be spliced onto the common exon 2. Exon 1D- and 1E-containing transcripts were confirmed by direct sequencing of amplimers from reverse transcriptase-coupled PCR. RNase protection studies revealed that one of these transcripts was expressed in mGR(++) cells only, but not in two mGR-less (mGR(--) S-49, and AtT-20 mouse pituitary) cell lines. These studies suggest that at least four promoters may be responsible for the control of GR (iGR and mGR) types in mouse lymphoma cells.
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PMID:Multiple glucocorticoid receptor transcripts in membrane glucocorticoid receptor-enriched S-49 mouse lymphoma cells. 1041 43

The peroxisome proliferator-activated receptor alpha (PPARalpha) plays a key role in lipid and lipoprotein metabolism. However, important inter- and intraspecies differences exist in the response to PPARalpha activators. This incited us to screen for PPARalpha variants with different signaling functions. In the present study, using a RT-PCR approach a variant human PPARalpha mRNA species was identified, which lacks the entire exon 6 due to alternative splicing. This deletion leads to the introduction of a premature stop codon, resulting in the formation of a truncated PPARalpha protein (PPARalphatr) lacking part of the hinge region and the entire ligand-binding domain. RNase protection analysis demonstrated that PPARalphatr mRNA is expressed in several human tissues and cells, representing between 20-50% of total PPARalpha mRNA. By contrast, PPARalphatr mRNA could not be detected in rodent tissues. Western blot analysis using PPARalpha-specific antibodies demonstrated the presence of an immunoreactive protein migrating at the size of in vitro produced PPARalphatr protein both in human hepatoma HepG2 cells and in human hepatocytes. Both in the presence or absence of 9-cis-retinoic acid receptor, PPARalphatr did not bind to DNA in gel shift assays. Immunocytochemical analysis of transfected CV-1 cells indicated that, whereas transfected PPARalphawt was mainly nuclear localized, the majority of PPARalphatr resided in the cytoplasm, with presence in the nucleus depending on cell culture conditions. Whereas a chimeric PPARalphatr protein containing a nuclear localization signal cloned at its N-terminal localized into the nucleus and exhibited strong negative activity on PPARalphawt transactivation function, PPARalphatr interfered with PPARalphatr transactivation function only under culture conditions inducing its nuclear localization. Cotransfection of the coactivator CREB-binding protein relieved the transcriptional repression of PPARalphawt by PPARalphatr, suggesting that the dominant negative effect of PPARalphatr might occur through competition for essential coactivators. In addition, PPARalphatr interfered with transcriptional activity of other nuclear receptors such as PPARgamma, hepatic nuclear factor-4, and glucocorticoid receptor-alpha, which share CREB-binding protein/p300 as a coactivator. Thus, we have identified a human PPARalpha splice variant that may negatively interfere with PPARalphawt function. Factors regulating either the ratio of PPARalphawt vs. PPARalphatr mRNA or the nuclear entry of PPARalphatr protein should therefore lead to altered signaling via the PPARalpha and, possibly also, other nuclear receptor pathways.
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PMID:A truncated human peroxisome proliferator-activated receptor alpha splice variant with dominant negative activity. 1047 44


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