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:1.4.1.2 (glutamate dehydrogenase)
4,380 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Eukaryotic chromatin is thought to be organized into independently regulated loop domains by interaction of matrix-attachment regions (MAR) of the DNA to the nuclear matrix. To define the borders of the chromatin loop containing the glutamate dehydrogenase (GDH) gene, we screened the GDH gene and flanking regions for the presence of MAR sequences. We here report identification, mapping and sequencing of an (A + T)-rich MAR located 2010-1397 bp upstream of the transcription initiation site of GDH, that mediates strong binding to the nuclear matrix. Smaller regions can also confer binding capacity, although at a lower affinity. This (A + T)-rich MAR contained 11 bp and 12 bp (A + T)-rich direct repeats, but not any of the sequences previously described to be associated with MAR activity. We here show that the presence of (A + T)-rich domains of DNA is not sufficient to confer binding capacity, since (A + T)-rich sequences located downstream of the identified MAR did not bind to the nuclear matrix. Moreover, a consensus topoisomerase-II-binding site located downstream of the MAR was found to be insufficient to mediate substantial binding. The number of binding sites in the nuclear matrix for MAR-containing fragments was shown to be approximately 15,000/nucleus. Since organization of the entire rat genome in loops with an average loop size of 100 kbp would require 60,000 binding sites, this suggests that only part of the genome is organized in loops. Alternatively, we might have underestimated the number of binding sites. The GDH MAR, and MAR-containing fragments derived from other species, were found to bind to the same binding sites in the nuclear matrix, although the affinity varied.
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PMID:Identification and analysis of a matrix-attachment region 5' of the rat glutamate-dehydrogenase-encoding gene. 835 85

gdhA1 is a spontaneous mutant of Escherichia coli that causes complete loss of activity of the NADP-specific glutamate dehydrogenase (GDH) encoded by the gdhA gene. The gdhA1 mutational site has been identified by recombinational mapping, polymerase chain reaction (PCR) amplification and DNA sequencing, as an A to G transition at nucleotide 274 of the gdhA coding sequence, resulting in an amino acid change of lysine 92 to glutamic acid. The mutant enzyme forms hybrid hexamers with a wild-type GDH, providing a useful system for analysis of conformational integrity of mutational variants.
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PMID:The gdhA1 point mutation in Escherichia coli K12 CLR207 alters a key lysine residue of glutamate dehydrogenase. 835 60

Tad is a LINE-like DNA element found in Neutrospora crassa. A Neurospora artificial intron based on the first intron of the am (glutamate dehydrogenase) gene was constructed and introduced, in the correct orientation, into a unique Nru I site in open reading frame 1 of an active Tad element, Tad1-1. Transformants containing the Tad element with the artificial intron were placed in forced heterokaryons with strains lacking Tad elements. Tad was shown to transpose between nuclei in these heterokaryons. Examination of the transposed Tad elements showed that the intron had been precisely removed in all cases. This confirms that Tad is a retrotransposon and that there is a cytoplasmic phase in these retrotransposition events.
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PMID:Transnuclear retrotransposition of the Tad element of Neurospora. 841 11

Purified rat pancreatic insulin-producing B-cells, which display a 12-fold higher activity of FAD-linked glycerophosphate dehydrogenase than other islet endocrine cells, were exposed for 30 min to 2 mM streptozotocin and subsequently cultured for 2 days in the absence or presence of 2 mM nicotinamide. Streptozotocin decreased by 54% the number of B-cells and, in surviving cells, lowered by 75% the activity of FAD-linked glycerophosphate dehydrogenase, whilst failing to affect that of glutamate dehydrogenase. This coincided with a 42-51% reduction of insulin secretion, when expressed relative to either the DNA or hormonal content of surviving cells. After exposure to streptozotocin, the presence of nicotinamide in the culture medium reduced cell death by 44% and also reduced the deleterious effects of streptozotocin upon both the enzymic and secretory activities of surviving cells. These findings indicate that the decreased activity of FAD-linked glycerophosphate dehydrogenase previously documented in pancreatic islets from streptozotocin-injected rats, as well as the protective effect of nicotinamide thereupon, are not attributable solely to changes in the number of B-cells but also to an altered enzymic activity in surviving B-cells. The latter anomaly may account, in part at least, for an impaired B-cell secretory response to D-glucose.
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PMID:Effect of streptozotocin and nicotinamide upon FAD-glycerophosphate dehydrogenase activity and insulin release in purified pancreatic B-cells. 848 53

Isolated proximal tubular (PT) and distal tubular (DT) cells from rat kidney were cultured for up to 9 days under serum-free, hormonally-defined conditions on 35-mm polystyrene culture dishes. Several hormonal and growth factor supplements were assessed for their ability to promote growth (increased protein and DNA content) and stability of differentiated phenotype (high activities of gamma-glutamyltransferase and alkaline phosphatase as brush-border membrane markers in PT cells; maintenance of high activities of glutamate dehydrogenase as a mitochondrial marker in both PT and DT cells; maintenance of low and high activities of lactate dehydrogenase in PT and DT cells, respectively; expression of cytokeratins). Basal supplemented media (DMEM/F12, 1:1 v/v) contained insulin, hydrocortisone, epidermal growth factor, sodium selenite and transferrin as supplements. Additionally, triiodothyronine selectively promoted growth and stability of differentiated phenotype in PT cells and thyrocalcitonin selectively promoted growth and stability of differentiated phenotype in DT cells. On Day 3 of primary culture, PT and DT cells were incubated for up to 8 h with either tert-butyl hydroperoxide (tBH; 0.5-10 mM), methyl vinyl ketone (MVK; 1-10 mM), or p-aminophenol (PAP; 1-10 mM) and cellular injury, as assessed by cellular release of lactate dehydrogenase, was determined. DT cells were significantly more susceptible to injury from both tBH and MVK, but the two cell populations were equally susceptible to injury from PAP, which is the same susceptibility pattern seen in freshly isolated cells. These results suggest that primary cultures of rat renal PT and DT cells reflect similar biochemical properties as freshly isolated cells and are, therefore, useful models for study of chemically induced injury.
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PMID:Susceptibility of primary cultures of proximal tubular and distal tubular cells from rat kidney to chemically induced toxicity. 854 48

Sixty-one isolates and collection strains of Aspergillus fumigatus were compared for their phenotypic (morphological features and isoenzyme profiles) and genotypic (restriction enzyme-generated mitochondrial DNA and ribosomal DNA profiles and random amplified polymorphic DNA patterns) features. The examined strains exhibited highly variable colony morphologies and growth rates at different temperatures, but their micromorphologies and conidial diameters were characteristic of the species. Of the isoenzymes studied, the beta-arylesterase and phosphatase patterns were the most divergent, and the 61 strains could be classified into seven groups. The glucose 6-phosphate dehydrogenase and catalase isoenzyme patterns displayed only a limited variability, while the profiles of superoxide dismutase, lactate dehydrogenase, and glutamate dehydrogenase were highly conserved. The HaeIII-generated mitochondrial DNA patterns and SmaI-digested repetitive DNA and ribosomal DNA hybridization patterns of almost all strains were also invariable. The level of variation was much higher when random amplified polymorphic DNA analysis was applied. Although the patterns of the strains were very similar with most of the primers, the application of some primers made it possible to cluster the A. fumigatus isolates into several groups. The results indicate that the random amplified polymorphic DNA technique could be used more efficiently than isoenzyme analysis for typing A. fumigatus isolates. A good correlation was found between the dendrograms obtained from the isoenzyme and random amplified polymorphic DNA data, but the isoenzyme and amplified DNA patterns did not correlate with the pathogenicity, pigment production, or geographical origin of the strains. One "A. fumigatus" strain (strain FRR 1266) exhibited unique isoenzyme, mitochondrial DNA, ribosomal DNA, and random amplified polymorphic DNA patterns; it is proposed that this strain represents a new species of the section Fumigati.
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PMID:Phenotypic and genotypic analysis of variability in Aspergillus fumigatus. 856 84

Acinetobacter baumannii, unnamed Acinetobacter species 3 (studied by P.J.M. Bouvet and P.A.D. Grimont) and unnamed DNA group 13 (studied by I. Tjernberg and J. Ursing) are the most prevalent Acinetobacter species in hospitals. Using the identification scheme of Bouvet and Grimont, it is sometimes difficult to differentiate these species from A. calcoaceticus sensu stricto, a species of the natural environment that has seldom been found associated with human infection. Genetically identified Acinetobacter isolates belonging to A. calcoaceticus sensu stricto (n = 12), A. baumannii (n = 22), Acinetobacter species 3 (n = 15) and DNA group 13 of Tjernberg and Ursing (n = 26), Acinetobacter species 10 (n = 2), Acinetobacter species 11 (n = 2) and 3 strains ungrouped by DNA-DNA hybridization were investigated for electrophoretic separations of L-malate dehydrogenase (MDH), glutamate dehydrogenase (GDH) and catalase (CAT). All A. calcoaceticus sensu stricto isolates were easily differentiated from those of other species investigated by their high MDH values (relative mobility (Rf) = 78), their low GDH values (Rf range: 24-28) and CAT values (Rf range: 34-42). Acinetobacter species 3 was differentiated from A. baumannii and DNA group 13 of Tjernberg and Ursing by high CAT values. A. baumannii could not be differentiated from Tjernberg and Ursing DNA group 13. Acinetobacter species 10 was clearly differentiated from Acinetobacter species 11. Once an Acinetobacter is phenotypically identified with the four closely related species investigated here, electrophoretic analysis of MDH, GDH and CAT might be a useful complement to the identification scheme of Bouvet and Grimont for accurately identifying A. calcoaceticus sensu stricto.
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PMID:Differentiation of Acinetobacter calcoaceticus sensu stricto from related Acinetobacter species by electrophoretic polymorphism of malate dehydrogenase, glutamate dehydrogenase and catalase. 858 99

In a chronic toxicity study in the rat, bidisomide administered as a dietary admixture produced a dose-related lowering of reticulocytes and leucocytes. Plasma alanine aminotransferase activity was increased at 300 mg/kg and decreased at 900 mg/kg. The potential mechanisms of these effects were investigated by comparing the responses in groups of male Sprague-Dawley rats receiving a control diet, or 300 or 1200 mg/kg/day bidisomide. Subsets of these groups were co-treated subcutaneously with folinic acid or with a vitamin B1, B6, B12 complex. Subsets of control and 300 mg/kg groups were maintained on a 20-25% feed restriction regimen for 3 months, to mimic the depression in body weight gain observed in animals receiving 1200 mg/kg. Body weight gains were significantly reduced at 1200 mg/kg and in all feed-restricted animals. Plasma and liver alanine aminotransferase (ALT) and plasma aspartate aminotransferase (AST) levels were also reduced at this dose level. At 300 mg/kg, plasma transaminases, glutamate dehydrogenase (GLDH) and sorbitol dehydrogenase (SDH) activities were increased. These changes were prevented in animals receiving folinic acid supplementation. Plasma glucose, triglycerides, and unsaturated and total iron binding capacities were decreased, while plasma iron levels tended to increase, mainly at the high dose. Vitamin supplementation prevented a decrease in reticulocyte counts at 300 mg/kg. Bidisomide increased urinary formimino-glutamic acid (FIGLU) excretion but did not affect methylmalonic acid (MMA) or taurine excretion. The effect on FIGLU at 1200 mg/kg was prevented by folinic acid co-treatment. Absolute liver weight was lowered at both dose levels and in feed-restricted animals. However, the relative liver weights were unaffected. Thymidine kinase and thymidylate synthase activity of the bone marrow cells were not altered by the bidisomide treatment. Except for the increase in plasma transaminase, GLDH and SDH levels at 300 mg/kg, changes in clinical chemistry parameters are considered to result mainly from nutritional restrictions. Changes in hematologic parameters appear to be related to the combination of decreased feed consumption (leukocytes) and decreased availability or utilization of folates (reticulocytes). This alteration, however, did not affect DNA synthesis in bone marrow. The prevention by folinic acid, but not by feed restriction, of the elevation of liver enzymes at 300 mg/kg is an intriguing, yet unexplained finding. There was no evidence that bidisomide affected B6 and B12 availability.
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PMID:Effect of folate supplementation on clinical chemistry and hematologic changes related to bidisomide administration in the rat. 858 20

Samples of DNA from a panel of Giardia isolated from humans and animals in Europe and shown previously to consist of 2 major genotypes--'Polish' and 'Belgian'--have been compared with human-derived Australian isolates chosen to represent distinct genotypes (genetic groups I-IV) defined previously by allozymic analysis. Homologous 0.52 kilobase (kb) segments of 2 trophozoite surface protein genes (tsa417 and tsp11, both present in isolates belonging to genetic groups I and II) and a 1.2 kb segment of the glutamate dehydrogenase (gdh) gene were amplified by the polymerase chain reaction (PCR) and examined for restriction fragment length polymorphisms (RFLPs). Of 21 'Polish' isolates that were tested, all yielded tsa417-like and tsp11-like PCR products that are characteristic of genetic groups I or II (15 and 6 isolates respectively) in a distinct assemblage of G. intestinalis from Australia (Assemblage A). Conversely, most of the 19 'Belgian' isolates resembled a second assemblage of genotypes defined in Australia (Assemblage B) which contains genetic groups III and IV. RFLP analysis of gdh amplification products showed also that 'Polish' isolates were equivalent to Australian Assemblage A isolates (this analysis does not distinguish between genetic groups I and II) and that 'Belgian' isolates were equivalent to Australian Assemblage B isolates. Comparison of nucleotide sequences determined for a 690 base-pair portion of the gdh PCR products revealed > or = 99.0% identity between group I and group II (Assemblage A/'Polish') genotypes, 88.3-89.7% identity between Assemblage A and Assemblage B genotypes, and > or = 98.4% identity between various Assemblage B/'Belgian' genotypes. The results confirm that the G. duodenalis isolates examined in this study (inclusive of G. intestinalis from humans) can be divided into 2 major genetic clusters: Assemblage A (= 'Polish' genotype) containing allozymically defined groups I and II, and Assemblage B (= 'Belgian' genotype) containing allozymically defined groups III and IV and other related genotypes.
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PMID:Molecular genetic analysis of Giardia intestinalis isolates at the glutamate dehydrogenase locus. 858 93

Recently, cases of liver damage and liver tumors have been reported after treatment of prostate cancer patients with the antiandrogen cyproterone acetate (CPA). In rat liver, CPA initiates a wave of DNA synthesis that is accompanied by apoptosis. In apoptotic hepatocytes, a latent form of transforming growth factor beta 1 (TGF-beta 1) is detectable by immunohistochemistry. Injection of a single dose of TGF-beta 1 induces apoptosis in the liver of animals pretreated with CPA but has an insignificant effect in untreated animals. In this study, we show by Northern analysis that there is increased expression of TGF-beta 1 in the liver after CPA treatment. Detection of TGF-beta 1 with in situ hybridization showed that TGF-beta 1 was synthesized in the parenchymal cells. Time course and dose-response experiments performed 48 hours after the last application of CPA showed that apoptotic nuclei with chromatin condensed at the nuclear periphery (AN) were already visible 2 hours after injection (0.13%), and apoptotic bodies (ABs) increased 2 to 9 hours after the injection (from 1.28% to 6.67%) after 25 micrograms TGF-beta 1/kg. At 4.5 hours after injection, an induction of apoptosis could be detected with 0.25 microgram TGF-beta 1/kg and after the maximum dose (250 micrograms TGF-beta 1/kg) ANs (0.24%) and ABs (16.74%) were homogeneously distributed throughout the liver lobe. Irrespective of the dose or time after injection of TGF-beta 1, 82% of the ABs were localized within hepatocytes. Liver enzymes were detected in high amounts in the serum (eightfold elevation of glutamate dehydrogenase, fivefold elevation of alanine transaminase [ALT]) 7 hours after the first visible sign of apoptosis. After an additional 20 hours, the liver contained many necrotic figures. These results suggest that the combination of TGF-beta 1 expression coupled with a strikingly enhanced sensitivity to the induction of apoptosis could be responsible both for the liver damage and the development of liver tumors observed after treatment with CPA.
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PMID:The antiandrogen cyproterone acetate induces synthesis of transforming growth factor beta 1 in the parenchymal cells of the liver accompanied by an enhanced sensitivity to undergo apoptosis and necrosis without inflammation. 859 60


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