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)

It is now widely accepted that many receptors are regulated by phosphorylation. The glutamate receptor which belongs to a family of AMPA receptors has recently been cloned and contains in the long intracellular loop several consensus phosphorylation sites for Ca(2+)-calmodulin-dependent protein kinase type II and protein kinase C. In order to study the possible function of these phosphorylation sites antibodies are specifically raised against these sites. For this purpose the DNA encoding the long intracellular loop was synthesized by PCR amplification from rat cerebral cortex and hippocampus RNA. Primer sequences were taken from the published receptor cDNA and the resulting inserts showed after sequence determination the presence of different receptor isoforms. The proteins have been expressed by the T7 RNA polymerase system. These can then be used after purification to generate antibodies against the entire protein and partial peptides both in a phosphorylated and unphosphorylated form.
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PMID:Cloning of the long intracellular loop of the AMPA-selective glutamate receptor for phosphorylation studies. 838 64

In this study, we isolated two cDNA molecules encoding putative glutamate receptor subunits, fGluR1 alpha and fGluR1 beta, from an Oreochromis sp. brain cDNA library by hybridizing with the glutamate receptor cDNA, fGluR2 beta, of the same fish. The deduced amino acid sequence of the fGluR1 alpha consists of 908 residues with an 18-residue signal peptide and displays a sequence identity of 74% to the amino acid sequence of rat GluR1 subunit. Northern blotting indicates that the expression level of fGluR1 alpha in telencephalon is higher than that in optic tectum and cerebellum in adult fish brain. Reverse-transcriptase polymerase chain reaction and genomic analyses reveal the presence of variants created by alternative splicing at the flip-flop module and the carboxyl terminus of fGluR1 alpha transcripts. The amino acid sequence of fGluR1 alpha is unique in that it contains a glutamine-rich sequence inserted at the loop 1 (L1) between transmembrane domains 1 and 2. A second incomplete cDNA clone, designated fGluR1 beta, coding for a polypeptide showing sequence identity to the rat GluR1 and fGluR1 alpha was isolated from the same library. Insertion of a serine- and glutamine-rich sequence at the L1 was also detected in the translated sequence of fGluR1 beta.
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PMID:Molecular analysis of cDNA molecules encoding glutamate receptor subunits, fGluR1 alpha and fGluR1 beta, of Oreochromis sp. 883 30

Here we report the cloning and functional analysis of a cDNA encoding a functional glutamate receptor subunit of Oreochromis sp., a freshwater teleost fish. The deduced amino acid sequence of this cDNA clone, fGluR3 alpha, displays the highest sequence identity to that of the mammalian GluR3 subunit. Results of quantitative reverse-transcriptase polymerase chain reaction (RT-PCR) analysis indicated that the expression level of fGluR3 alpha in the cerebellum was much less than that in the telencephalon and optical lobe. Similar to its mammalian counterpart, variants of fGluR3 alpha were created by alternative splicing and RNA editing at the R/G site. The channel properties of homomeric fGluR3 alpha expressed in Xenopus oocytes were similar to those of the mammalian alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)-preferring receptors. The rank order of agonist potency of the expressed fGluR3 alpha is AMPA > or = glutamate > or = quisqualate > domoate > or = kainate. This is the first functional glutamate receptor of teleost fish being demonstrated to be sensitive to AMPA. Furthermore, this study suggested a strong functional conservation of AMPA-preferring receptors in vertebrates.
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PMID:Molecular and electrophysiological characterizations of fGluR3 alpha, an ionotropic glutamate receptor subunit of a teleost fish. 967 19

The ability of metabotropic glutamate receptor activation to mobilise intracellular calcium was investigated in cultured dorsal root ganglion (DRG) neurones from neonatal rats using the calcium sensitive fluorescent dye Fura-2. L-glutamate (10 microM) caused sustained and oscillatory increases in intracellular calcium concentration ([Ca2+]i) in a subpopulation of cultured DRG neurones. The oscillatory responses were not blocked by combined application of the ionotropic glutamate receptor antagonists MK 801 (2 microM) and CNQX (20 microM). Oscillations in [Ca2+]i were also observed following application of the nonselective metabotropic glutamate receptor (mGluR) agonist, trans-(1S,3R)-1-aminocyclopentane-1S, 3R-dicarboxylic acid (1S,3R)-ACPD, 20 microM) and the mGluR5 agonist (RS)-2-chloro-5-hydroxyphenylglycine (CHPG, 500 microM). These responses were blocked by the selective Group I mGluR antagonist (RS)-1-aminoindan-1,5-dicarboxylic acid (AIDA) (100 microM) and Ca2+ release channel inhibitors ryanodine (100 microM) and dantrolene (10 microM). The predominantly Group II agonist (2S,2'R,3'R)-2-(2'3'-dicarboxy-cyclopropyl)glycine (DCG-IV, 100 microM) failed to produce Ca2+ transients alone but suppressed responses to CHPG. Reverse transcriptase PCR techniques, using primers specific to Group I mGluRs, revealed the presence of mGluR5 but not mGluR1 mRNA in these cells. Therefore, glutamate can cause a slowly activating and reversible mobilisation of [Ca2+]i in sensory neurones by activation of ionotropic receptors, and can induce oscillatory calcium transients by selectively activating metabotropic glutamate receptors that are likely to be of the mGluR5 subtype.
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PMID:Mobilisation of intracellular Ca2+ by mGluR5 metabotropic glutamate receptor activation in neonatal rat cultured dorsal root ganglia neurones. 1072 83

The AMPA receptor (AMPAR), a pharmacologically defined ionotropic glutamate receptor, mediates fast excitatory synaptic transmission in the vertebrate central nervous system. Mammalian and avian AMPARs are assembled from the products of four genes (GRIA1-GRIA4) conserved in their translated sequences and gene organizations. Teleost fish also express AMPAR subunits; however, the AMPAR genes have not been extensively investigated in lower vertebrates. To elucidate the evolution of vertebrate AMPAR genes, reverse-transcriptase PCR-based surveys of subunits expressed in the brains of eight nonmammalian vertebrates were performed. The newly cloned vertebrate AMPAR subunits were classified by their sequence identities to the mammalian AMPAR subunits. The results of molecular and phylogenetic analyses indicated that the members of the AMPAR gene family increased from two in the jawless hagfish to four in the tetrapods and the shark and to more than four in the teleost fish. The sizes of AMPAR gene families correlate well with those of many multigene families observed in various vertebrates. Moreover, all vertebrates expressed at least one AMPAR subunit bearing an arginine (R) at the Q/R site, at which no invertebrate glutamate receptor subunit has been found to have an R residue, suggesting that the low calcium-permeable AMPARs appeared at early evolutionary stages of vertebrate central nervous systems. Uniquely, the loop 1 (L1) regions between hydrophobic domain 1 and hydrophobic domain 2 of the hagfish putative GRIA2 and all the teleost GRIA1 subunits were much longer than those of the remaining known ionotropic glutamate receptor subunits. The length and sequence of the L1 of teleost GRIA1 subunits were heterogeneous, suggesting that the amino acid residues in L1 were not highly selected.
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PMID:Identifications, classification, and evolution of the vertebrate alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor subunit genes. 1167 29

The influence of activation of glutamate receptor (GluR) on outward K(+) current in cultured neonate rat hippocampal astrocytes was investigated. Patch-clamp analysis of K(+) channel currents in cultured astrocytes identified the existence of 71 +/- 6 and 161 +/- 11 pS single-channel K(+) currents that were sensitive to changes in voltage and [Ca(2+)](i) and blocked by external TEA but not by charybdotoxin, iberiotoxin, apamin, or 4-aminopyridine. Reverse transcriptase (RT)-PCR and Northern blot analysis revealed transcripts of the Ca(2+)-activated K(+) channel (K(Ca)) beta(4)-subunit (beta4) (KCNMB4) in cultured astrocytes. Expression of the metabotropic glutamate receptor (mGluR) subtypes mGluR1 and mGluR5 and the ionotropic glutamate receptor (iGluR) subtypes iGluR1 and iGluR4 were detected by RT-PCR and immunofluorescence analysis in cultured astrocytes. The mGluR agonists L-glutamate and quisqualate increased the open state probability (NP(o)) of the 71 and 161 pS K(+) channel currents that were prevented by the mGluR receptor antagonists 1-aminoindan-1,5-dicarboxylic acid or L-(+)-2-amino-3-phosphonopropionic acid and not by the iGluR antagonists (+)-5-methyl-10,11-dihydro-5H-dibenzo [a,d] cyclohepten-5,10-imine maleate or CNQX. Activation of the two types of K(+) channel currents by mGluR agonists was attenuated by pertussis toxin and by inhibition of phospholipase C (PLC) or cytochrome P450 arachidonate epoxygenase. These results indicate that brain astrocytes contain the KCNMB4 transcript and express two novel types of K(Ca) channels that are gated by activation of a G-protein coupled metabotropic glutamate receptor functionally linked to PLC and cytochrome P450 arachidonate epoxygenase activity.
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PMID:Metabotropic glutamate receptor activation enhances the activities of two types of Ca2+-activated k+ channels in rat hippocampal astrocytes. 1262 72

Cerebellar repetitive transcranial magnetic stimulation (rTMS) has been applied to treat several pathological conditions with insufficient evidence of molecular mechanism. Neural plasticity is proposed as one of mechanism. This study aimed to (1) confirm the feasibility of focal stimulation over cerebellar cortex and (2) investigate cerebellar rTMS effects on molecular changes associated with neural plasticity in the rat. For feasibility, six male Sprague-Dawley rats underwent (18)F-FDG positron emission tomography (PET) to confirm focal stimulation on the cerebellar cortex after rTMS. For molecular evidence, thirty rats underwent a single (N=15) or 10 sessions (N=15) of rTMS with low-, high-frequency, or sham stimulation. In cerebellar cortex, reverse-transcriptase polymerase chain reaction and western blotting were performed on mRNA and proteins associated with neural plasticity: metabotrophic glutamate receptor 1 (GluR1), 2-amino-5-methyl-4-isoxazole-propionatic acid (AMPA) receptor (GluR2) and protein kinase C (PKC). As a result, (18)F-FDG-PET showed an increase of glucose metabolism in the cerebellar cortex. The transcription of mGluR1 decreased following a single session of high-frequency rTMS. Synthesis of mGluR, PKC and GluR2 was reduced after rTMS, especially high frequency stimulation. It is suggested that rTMS could focus on the cerebellar cortex in the rat and induce neural plasticity associated with long-term depression.
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PMID:The molecular evidence of neural plasticity induced by cerebellar repetitive transcranial magnetic stimulation in the rat brain: a preliminary report. 2486 5

Enhanced receptiveness at all synapses on a neuron that receive glutamatergic input is called cell-wide synaptic upscaling. We hypothesize that this type of synaptic plasticity may be critical for long-term memory storage within cortical circuits, a process that may also depend on epigenetic mechanisms, such as covalent chemical modification of DNA. We found that DNA cytosine demethylation mediates multiplicative synaptic upscaling of glutamatergic synaptic strength in cultured cortical neurons. Inhibiting neuronal activity with tetrodotoxin (TTX) decreased the cytosine methylation of and increased the expression of genes encoding glutamate receptors and trafficking proteins, in turn increasing the amplitude but not frequency of miniature excitatory postsynaptic currents (mEPSCs), indicating synaptic upscaling rather than increased spontaneous activity. Inhibiting DNA methyltransferase (DNMT) activity, either by using the small-molecule inhibitor RG108 or by knocking down Dnmt1 and Dnmt3a, induced synaptic upscaling to a similar magnitude as exposure to TTX. Moreover, upscaling induced by DNMT inhibition required transcription; the RNA polymerase inhibitor actinomycin D blocked upscaling induced by DNMT inhibition. Knocking down the cytosine demethylase TET1 also blocked the upscaling effects of RG108. DNMT inhibition induced a multiplicative increase in mEPSC amplitude, indicating that the alterations in glutamate receptor abundance occurred in a coordinated manner throughout a neuron and were not limited to individual active synapses. Our data suggest that DNA methylation status controls transcription-dependent regulation of glutamatergic synaptic homeostasis. Furthermore, covalent DNA modifications may contribute to synaptic plasticity events that underlie the formation and stabilization of memories.
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PMID:DNA methylation regulates neuronal glutamatergic synaptic scaling. 2610 19

Adamantinomatous craniopharyngioma (ACP) is a congenital epithelial tumor in the sellar region with benign histological manifestation but invasive. Currently, surgery is the main treatment for it, but its recurrence rate is high. Therefore, it is of great importance to explore the mechanism of occurrence and development of ACP and to identify new molecules. One gene expression profile, GSE94349, was downloaded from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) were identified by the limma package. Gene set enrichment analysis was used to make enrichment analysis using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Then, we performed the construction and analysis of the protein-protein interaction (PPI) network and significant module. The analysis of the GSE94349 dataset identified 109 DEGs, consisting of 80 upregulated genes and 29 downregulated genes in ACP samples compared with normal brain tissues. Functional and pathway enrichment analysis of DEGs provided a comprehensive overview of some major pathophysiological mechanisms in ACP: RNA polymerase II promoter, glutamate receptor binding, and so on. A total of 10 hub genes of DEGs were obtained from the PPI network, which provided potential therapeutic targets for the ACP. In summary, there were DEGs between ACP tissues and normal brain tissues, which may be involved in the mechanisms of occurrence and development of ACP, especially via the regulation of RNA polymerase II promoter and glutamate receptor binding. Key genes in DEGs could serve as new research targets for the diagnosis and treatment of ACP.
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PMID:Identification and Functional Enrichment Analysis of Potential Diagnostic and Therapeutic Targets in Adamantinomatous Craniopharyngioma. 3142 86

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