Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.1.99.3 (PRE)
 1,923 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The myelin (My) basic protein-encoding gene (MBP) is specifically expressed by oligodendrocytes (OL) in the central nervous system (CNS) and by Schwann cells in the peripheral nervous system (PNS). To define cell-type-specific regulatory elements, a series of chimaeric constructs containing varying lengths of the 5'-flanking region and exon 1 of MBP linked to the cat reporter gene was transfected into several cell types, including primary cultures of differentiated rat OL, Schwann cells and kidney cells, as well as neuronal and non-neuronal cell lines. All the constructs generated variable levels of chloramphenicol acetyltransferase (CAT) activity in all cell types, except in primary OL and Schwann cells, where distinct positive (PRE) and negative regulatory elements (NRE) were found to be involved in regulating cat expression. The nucleotide (nt) -53/+70 construct gave maximal activity in all cell types, except OL and Schwann cells, where sequences upstream from nt -53 were necessary for maximal promoter activity. The sequences located at nt -655 to -397 and nt -394 to -54 showed enhancer and repressor effects, respectively, in OL. In Schwann cells, sequences from -394 to -253 showed positive regulatory effects, while those between -655 to -397 and -253 to -54 showed negative regulatory effects. In the downstream region of the promoter, sequences from +20 to +70 and +70 to +200 showed strong silencer and enhancer activities specifically in OL. In gel-retardation assays using nuclear extracts prepared from several cell types and the -253 to -53 repressor sequences, specific DNA-protein complexes unique to OL were identified.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Regulation of myelin basic protein-encoding gene transcription in rat oligodendrocytes. 752 38

Using a DNA-protein binding assay, we have previously identified and characterized a UV-damaged DNA recognition protein (UVDRP) from HeLa cells [(1991) Nucleic Acids Res. 19, 6413-6418]. In this report, the photoreactivating activity of UVDRP from the yeast, Saccharomyces cerevisiae, and HeLa cells was investigated. Although yeast and human cells are evolutionarily different from each other, both UVDRPs were conserved in the sense of their biochemical characteristics except that the yeast UVDRP also exhibited an enzymatic photoreactivating activity. A mammalian expression vector plasmid DNA carrying the bacterial chloramphenicol acetyltransferase (CAT) gene was UV irradiated in vitro followed immediately by exposure to photoreactivating light, and its transient expression in repair-deficient xeroderma pigmentosum (XP) cells was investigated. More than 80% of the CAT activity was inhibited by UV irradiation, which was partially restored (> 60%) by a partially purified yeast photolyase. In contrast, HeLa cell extracts did not express a photoreactivatable recovery from UV-induced inhibition of the CAT activity tested in the same system. This study has demonstrated the potential use of the DNA-mobility shift assay to investigate enzymatic photoreactivation, and has indicated the absence of the repair mechanism in human cells.
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PMID:Lack of DNA enzymatic photoreactivation in HeLa cell-free extracts. 828 3

It has been shown previously that sigma receptor agonists reveal potential antidepressant activity in experimental models. Moreover, some data indicate sigma receptor contribution to stress-induced responses (e.g., conditioned fear stress in mice), though the mechanism by which sigma ligands can exert their effects, remains unclear. Recent studies have indicated that antidepressant drugs (ADs) inhibit glucocorticoid receptor (GR) function in vitro. The aim of the present study was to find out whether sigma receptor ligands are able to directly affect GR action. To this end, we evaluated the effect of sigma receptor agonists and antagonists on GR function in mouse fibroblast cells (L929) stably transfected with mouse mammary tumor virus-chloramphenicol acetyltransferase (MMTV-CAT) plasmid (LMCAT cells). For this study, we chose SA4503, PRE 084, DTG (selective sigma(1) or sigma(1/2) receptor agonists) and BD 1047, SM 21, rimcazole (sigma receptor antagonists). Fluvoxamine, the selective serotonin reuptake inhibitor with sigma(1/2) receptor affinity, was used for comparison. It was found that SM 21 (at 1, 3, 10 and 30 microM), BD 1047 (3, 10 and 30 microM) rimcazole (10 microM), and fluvoxamine (at 3, 10 and 30 microM) significantly inhibited corticosterone-induced gene transcription, while DTG, SA 4503 and PRE 084 remained ineffective. Thus, the sigma receptor agonists that predominantly showed antidepressant-like activity in behavioral models, were without effect in this in vitro model. These results suggest that antidepressant-like activity of sigma receptor agonists is independent of corticosterone-induced gene transcription. Therefore, the attenuation of GR function induced by sigma receptor antagonists remains ambiguous and requires further study.
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PMID:Effects of selective sigma receptor ligands on glucocorticoid receptor-mediated gene transcription in LMCAT cells. 1921 81