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:2.7.7.6 (RNA polymerase)
34,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lutropin and human choriogonadotropin stimulated the endogenous chromatin-associated polymerase activity in purified chromatin prepared from nuclei of bovine corpus luteum. Chromatin was incubated in two different buffer systems: one that mainly supports the activity of polymerase I, another that supports the activity of polymerase II and is largely alpha-amanitin sensitive. The hormones lutropin and chorigonadotropin stimulated an increase in the rate of incorporation of [14C]ATP or [14C]UTP into RNA in both buffer systems. Follitropin, prolactin and beta-corticotropin had no stimulatory effect. Neither the alpha nor beta subunit of lutropin stimulated RNA synthesis. When premixed, the subunits rapidly formed the active molecule. A maximum response to RNA synthesis was achieved by a 10(-9) M concentration of human choriogonadotropin. Considerable activity was obtained at 10(-11) M human choriogonadotropin. There was no lutropin stimulation to RNA synthesis using calf thymus DNA and Escherichia coli RNA polymerase.
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PMID:Lutropin stimulation of RNA synthesis in corpus luteum chromatin. 32 86

Adrenocortical cell major secreted protein was purified from the conditioned medium of primary cultures of bovine adrenocortical (BAC) cells. Immunochemical analysis and N-terminal sequencing of the purified protein identified it to alpha 2-macroglobulin (alpha 2-M). It appeared that 15 out of the 17 N-terminal amino acids were conserved between adrenocortical cell major secreted protein and human alpha 2-M. Study of alpha 2-M production by BAC cells revealed that its secretion was stimulated severalfold by transforming growth factor-beta 1 (TGF-beta 1). The stimulation occurred in a time-dependent (reaching a plateau at 24 h) and dose-dependent (ED50 = 0.1 ng/ml TGF-beta 1) manner. It was blocked when BAC cells were exposed to 5,6-dichlorobenzimidazole riboside, a potent inhibitor of RNA polymerase II, suggesting that TGF-beta 1 acts as an activator of alpha 2-M gene expression at the transcriptional level. Northern blot analysis confirmed that the alpha 2-M mRNA level was increased (4-fold) in BAC cells following TGF-beta 1 treatment. TGF-beta 2, TGF-beta 1,2, basic fibroblast growth factor, and angiotensin II also appeared able to stimulate alpha 2-M secretion in BAC cells, whereas adrenocorticotropin was strongly inhibitory. Given the previous reports that TGF-beta 1 is a potent inhibitor of adrenocortical steroidogenesis (Feige J.J., Cochet, C., Rainey, W.E., Madani, C., and Chambaz, E. M. (1987) J. Biol. Chem. 262, 13491-13495) and that alpha 2-M is a TGF-beta 1-binding protein, these observations suggest that alpha 2-M may play an important role in conjunction with hormones and growth factors in the homeostatic regulation of adrenocortical functions.
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PMID:Transforming growth factor-beta stimulates the expression of alpha 2-macroglobulin by cultured bovine adrenocortical cells. 168 94

L-Glutamic acid (gamma-4'-hydroxyanilide) (GHB) is oxidized by tyrosinase to a quinone which inhibits DNA polymerase, RNA polymerase, and mitochondrial energy production within mushrooms. It was previously shown that GHB can kill B16 melanoma cells in culture, but lacks cytotoxicity for nontyrosinase-containing cells. We have conjugated this drug to a superpotent melanotropic peptide and examined the bioactivity of this conjugate to melanoma cells. 4'-Hydroxyaniline was attached to glutamic acid at position 5 in the superpotent melanotropin fragment analogue, Ac-[Nle4, D-Phe7]alpha-MSH4-10-NH2. The melanotropin:anilide conjugate, Ac-[Nle4, Glu(gamma-4'-hydroxyanilide)5, D-Phe7]alpha-MSH4-10-NH2, was not cytotoxic to B16 or Cloudman S91 mouse melanoma cells in culture, as determined by cell counts and protein assays. Interestingly, we also found that GHB stimulated melanoma cell tyrosinase above control levels in both melanoma cell lines. In our study, GHB itself also was found not to be cytotoxic to B16 or S91 melanoma cells in culture. In the frog skin bioassay, the melanotropin conjugate was more potent than alpha-MSH or Ac-[Nle4, D-Phe7]alpha-MSH4-10 in stimulating melanosome dispersion. These results demonstrate that putative chemotherapeutic ligands can be incorporated into active-site fragment analogues of MSH without loss of biological activity.
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PMID:Synthesis and actions of a melanotropin conjugate, Ac-[Nle4, Glu(gamma-4'-hydroxyanilide)5, D-Phe7]alpha-MSH4-10-NH2, on melanocytes and melanoma cells in vitro. 216 79

Pro-opiomelanocortin (POMC) was expressed in CV-1 (green monkey kidney) cells using a vaccinia virus transient expression system [(1986) Proc. Natl. Acad. Sci. USA 83, 8122]. The system involved infection of cells with a recombinant vaccinia virus carrying the T7 RNA polymerase gene and transfection with a plasmid containing the mouse POMC sequence flanked by the T7 RNA polymerase promoter at its 5'-end and the T7 RNA polymerase terminator at its 3'-end. Assay of the medium from transfected cells showed that 1-2 micrograms of immunoreactive ACTH was produced/10(6) cells. Analysis of the same medium by SDS-PAGE/Western blots revealed a band of 30-36 kDa, which was immunostained with both ACTH and beta-endorphin antisera. Labeling the transfected cells with [3H]Arg, followed by immunoprecipitation and SDS-PAGE showed the synthesis of a major peak of POMC, 33 kDa. Purified [3H]POMC expressed by CV-1 cells was cleaved in vitro by bovine intermediate lobe secretory vesicle pro-opiomelanocortin-converting enzyme to ACTH intermediates (19-25 kDa), beta-lipotropin and beta-endorphin. Thus, this work has demonstrated a technique for expressing microgram quantities of prohormones in mammalian cells, suitable for use as substrates for prohormone-converting enzymes in vitro.
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PMID:Production of pro-opiomelanocortin (POMC) by a vaccinia virus transient expression system and in vitro processing of the expressed prohormone by POMC-converting enzyme. 254 89

The effects of corticotropin releasing factor (CRF) on pro-opiomelanocortin (POMC) gene expression were investigated in an anterior pituitary corticotrophic tumor cell line, AtT-20/D16-16. The results of mRNA dot blot hybridization assays suggested that CRF, at a concentration of 10(-7) M, positively regulates the expression of the POMC gene in AtT-20 cells in a concentration-dependent fashion. Evaluation of the time course of this effect indicated that CRF had a biphasic mode of action. CRF and alpha-amanitin (inhibitor of RNA polymerase II activity) were also found to affect POMC mRNA levels in a concentration-dependent fashion. Eight-bromo-cyclic adenosine monophosphate (8-Br-cAMP) produced biphasic effects on POMC mRNA levels, supporting evidence of a role for cAMP as a second messenger in the regulation of POMC gene expression. It was also found that alpha-amanitin negatively regulated basal and CRF-stimulated POMC mRNA levels at both the 2 hr and 24 hr time periods, supporting evidence for positive regulation of POMC by CRF at the transcriptional level.
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PMID:CRF and cAMP regulation of POMC gene expression in corticotrophic tumor cells. 282 45

The present study investigated whether diurnal variations in the secretion of alpha MSH and beta-endorphin from the intermediate lobe (IL) of the pituitary are associated with parallel changes in the synthesis of mRNA specifically encoding proopiomelanocortin (POMC). The results demonstrate that concomitant diurnal variations occur in both plasma and IL concentrations of immunoreactive beta-endorphin and alpha MSH. Plasma and IL peptide levels were relatively constant during daylight hours (0600-1800 h), but increased after the onset of darkness and reached maximal concentrations at 0200 h. To examine the possibility that this diurnal rhythm in the content and secretion of POMC-derived peptides resulted from diurnal changes in the biosynthesis of POMC, the concentration and rate of synthesis of POMC mRNA were examined. POMC mRNA levels were elevated during the dark period, reaching a maximum level at 0200 h that was 2-fold higher than that occurring during the light period. POMC mRNA synthesis, determined by measuring the number of RNA polymerase II complexes transcribing the POMC gene in isolated cell nuclei, also varied diurnally, with maximum transcription rates occurring at 1800 h, thus preceding maximal increases in POMC mRNA content and POMC peptide secretion by 8 h. Together, these data indicate that diurnal variations in the content and secretion of POMC-derived peptides are associated with parallel changes in POMC mRNA concentrations and are preceded by similar changes in POMC gene transcription.
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PMID:A diurnal rhythm in proopiomelanocortin messenger ribonucleic acid that varies concomitantly with the content and secretion of beta-endorphin in the intermediate lobe of the rat pituitary. 293 89

We investigated the regulatory influence of several cytokines on the expression of preproenkephalin (PPE) mRNA in human peripheral blood mononuclear cells (PBMC). By use of a quantitative reverse-transcriptase-polymerase chain reaction (RT-PCR), we demonstrate that the T helper 2 cytokines IL-4 and IL-10 are more potent in upregulating PPE mRNA expression in human PBMC than the T helper 1 cytokines IL-2 and gamma-IFN. In addition, TGF-beta is also an effective inducer of PPE mRNA. TGF-beta, IL-4 and IL-10 increase the cytoplasmatic concentration of met-enkephalin in PBMC. Secretion of met-enkephalin in the culture supernatant of IL-4- or IL-10-stimulated PBMC could not be observed, but proenkephalin A-derived met-enkephalin containing peptides could be demonstrated. IL-4 and IL-10 do not induce PPE mRNA via the same pathways. We could observe that PKA is involved in IL-4 mediated PPE mRNA induction, whereas IL-10 apparently uses another route.
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PMID:T helper 2 cytokines induce preproenkephalin mRNA expression and proenkephalin A in human peripheral blood mononuclear cells. 935 52

The regulatory effects of adrenocorticotropin (ACTH) at the adrenal cell nucleus are not yet completely clarified. Recent studies showed that eukaryotic cell nucleus is composed of specific subcompartments organized by the nucleoskeleton-nuclear matrix. In this paper, the RNA polymerase II transcriptional domains were detected in the adrenal nucleus after acute and chronic ACTH stimulation by using in situ hybridization. Polydeoxythymidine (poly-T) probe, complementary to the polyadenylated (poly-A) chain of all the mRNAs and its precursors, was used. Hybridization was performed in intact adrenal cells and in nuclear matrices isolated from previously dispersed cells. The transcriptional domains, enriched in poly-A RNA, were evident in intact adrenal cells, the staining intensity being higher both in the acutely and in the chronically stimulated animals. In the nuclear matrices poly-A-rich areas were still visible, and were more intensely stained after ACTH stimulation.
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PMID:Poly-A-rich domains in adrenal cell nuclear matrix after acute and chronic ACTH stimulation: an in situ hybridization study. 1107 18

Recently, overlapping molecular phenotypes of hematopoietic and neuropoietic cells were described in mice. Here, we examined primary human CD34(+) hematopoietic stem and progenitor cells applying specialized cDNA arrays, real-time reverse-transcriptase-polymerase chain reaction (RT-PCR), and fluorescent-activated cell sorter (FACS) analysis focusing on genes involved in neurobiologic functions. We found expression of vesicle fusion and motility genes, ligand- and voltage-gated ion channels, receptor kinases and phosphatases, and, most interestingly, mRNA as well as protein expression of G protein-coupled receptors of neuromediators (corticotropin-releasing hormone 1 [CRH 1] and CRH 2 receptors, orexin/hypocretin 1 and 2 receptors, GABAB receptor, adenosine A(2)B receptor, opioid kappa 1 and mu 1 receptors, and 5-HT 1F receptor). As shown by 2-color immunofluorescence, the protein expression of these receptors was higher in the more immature CD38(dim) than in the CD38(bright) subset within the CD34(+) population, and completely absent in fully differentiated blood cells, suggesting that those receptors play a role in developmentally early CD34(+) stem and progenitor cells. The intracellular concentration of cyclic adenosine monophosphate (cAMP) in CD34(+) cells was diminished significantly upon stimulation of either CRH or orexin receptors, indicating that those are functionally active and coupled to inhibitory G proteins in human hematopoietic cells. In conclusion, these findings suggest a molecular interrelation of neuronal and hematopoietic signaling mechanisms in humans.
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PMID:Primary human CD34+ hematopoietic stem and progenitor cells express functionally active receptors of neuromediators. 1501 51

We report that mice with a targeted null mutation in the interferon type I receptor (IFN-RI), which cannot respond to such IFNs as IFNalpha and IFNbeta, have a 30% reduction in time spent in spontaneous rapid eye movement sleep (REMS) as a consequence of a reduced number of REMS episodes. Time spent in nonrapid eye movement sleep (NREMS) was essentially unaltered in IFN-RI knockouts (KOs) compared to 129 SvEv controls. Body temperature and locomotor activity were similar in both strains of mice. Hypothalamic expression of mRNAs for molecules previously linked to sleep-wake regulation and an IFN-inducible antiviral gene, 2',5'-oligoadenylate synthetase 1a (OAS), were determined by real-time reverse-transcriptase polymerase chain reaction (RT2-PCR). The level of hypocretin A mRNA was elevated in IFN-RI KO mice compared to 129 SvEv mice, while prolactin mRNA and OAS mRNA levels were suppressed. Vasoactive intestinal peptide (VIP) and corticotropin-releasing hormone (CRH) mRNA levels were unchanged relative to controls. Serum prolactin levels were similar in both strains. Results are consistent with the hypothesis that increased hypocretin and reduced prolactin in the hypothalamus of IFN-RI KO mice are responsible for their reduced REMS. In addition, the reduced OAS expression may result in modulation of prolactin receptor signaling and thus contribute to suppression of REMS.
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PMID:Mice deficient in the interferon type I receptor have reduced REM sleep and altered hypothalamic hypocretin, prolactin and 2',5'-oligoadenylate synthetase expression. 1549 63


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