Disease relevance of Glul

• Inhibition of glutamine synthetase in the mouse kidney: a novel mechanism of adaptation to metabolic acidosis [1].
• From a rat genomic library in phage lambda Charon4A, a complete glutamine synthetase-encoding gene was isolated [2].
• This is especially the case for the induction of GS in hepatoma cells [3].
• These data suggest that the changes in activity and distribution of glutamine synthetase contribute to hyperammonemia in cirrhosis [4].
• When portacaval anastomosis rats were infused with ammonium acetate and pretreated with 150 mg/kg methionine-sulfoximine, an inhibitor of glutamine synthetase activity, brain edema was ameliorated and intracranial pressure did not rise [5].

Psychiatry related information on Glul

• Glutamine synthetase modulation in the brain of rats subjected to deprivation of paradoxical sleep [6].
• Effects of modafinil-induced wakefulness on glutamine synthetase regulation in the rat brain [7].
• The activities of alanine-, aspartate- and branched-chain amino-acid transaminases, glutamine synthetase, glutamate dehydrogenase and adenylate deaminase in white adipose tissue of adult male rats have been determined in animals submitted to 12-h cold exposure (4 degrees C) or to 24-h food deprivation [8].

High impact information on Glul

• Glutamine-stimulated modification and degradation of glutamine synthetase in hepatoma tissue culture cells [9].
• The activities of cyclic nucleotide phosphohydrolase, an enzyme marker for oligodendrocytes, and glutamine synthetase, an enzyme marker for astrocytes, were studied at early (21 to 26) and late (82 to 88) cell passages [10].
• Glutamine synthetase was found to be localized in the glial cells [11].
• Enzyme expression in the periportal region was not affected, but the pericentral rim of hepatocytes expressing glutamine synthetase, ornithine aminotransferase, and NADPH cytochrome P-450 reductase (CYPred) first declined in diameter, then became discontinuous, and finally disappeared [12].
• Antibody reactive with glutamine synthetase stained all fetal liver cells but almost all cells lost this antigen after birth; only a single layer of pericentral cells retained it in adulthood [13].

Chemical compound and disease context of Glul

• The activities of both the a (glucose 6-phosphate-independent) and b (glucose 6-phosphate-dependent) forms of GS were also lower in human and rat hepatomas than in the respective host livers [14].
• Cirrhosis induced in rats by carbon tetrachloride was used to study alterations in the activities and lobular distribution of carbamoylphosphate synthetase and glutamine synthetase [4].
• Methionine sulfoximine, a glutamine synthetase inhibitor, attenuates increased extracellular potassium activity during acute hyperammonemia [15].
• We have analyzed the responses of four different glucocorticoid-inducible proteins, tyrosine aminotransferase [L-tyrosine:2-oxoglutarate aminotransferase (EC 2.6.1.5)], glutamine synthetase [L-glutamate:ammonia ligase (EC 6.3.1.2)], a secreted glycoprotein Belt I, and the mouse mammary tumor virus (MMTV)-encoded protein (gp52) in these cells [16].
• Glutamate-induced glutamine synthetase expression in retinal Muller cells after short-term ocular hypertension in the rat [17].

Biological context of Glul

• In conclusion, LPS impairs hepatic ammonia detoxification by both downregulation of GS and its inactivation because of tyrosine nitration [18].
• Together with the finding via mass spectrometry that peroxynitrite-induced inactivation of purified GS is associated with nitration of the active site tyrosine residue, our data suggest that tyrosine nitration critically contributes to inactivation of the enzyme [18].
• These results strongly suggest that, in the mouse kidney, glutamine synthetase is an important regulatory component of the availability of the ammonium ions to be excreted for defending systemic acid-base balance [1].
• This silencer was designated GS silencer element of the rat [19].
• Nucleotide sequence of rat glutamine synthetase mRNA [20].

Anatomical context of Glul

• Glutamine synthetase (GS) in the liver is restricted to a small perivenous hepatocyte population and plays an important role in the scavenging of ammonia that has escaped the periportal urea-synthesizing compartment [18].
• In many tissues and cell lines, the synthetic glucocorticoid dexamethasone alone increases GS expression several fold [19].
• The distribution of glutamine synthetase in subcellular fractions of rat brain [21].
• Glutamine synthetase was found to be predominantly localized at the nerve terminal and a number of results suggested a possibble association with the synaptic membrane [21].
• Light and electron microscopic immunocytochemical localization of glutamine synthetase in the superficial pineal gland of the rat [22].

Associations of Glul with chemical compounds

• In line with GS inactivation, glutamine synthesis from ammonia (0.3 mmol/L) in perfused livers from 24-hour LPS-treated rats was decreased by approximately 50%, whereas urea synthesis was not significantly affected [18].
• Lipopolysaccharide-induced tyrosine nitration and inactivation of hepatic glutamine synthetase in the rat [18].
• The subcellular localization of glutamine synthetase, an enzyme fundamental to the compartmentation of glutamate hypothesis, was investigated using brain tissue of adult rats [21].
• Transient transfection of a variety of cell lines with deletion constructs of the glutamine synthetase promoter driving a chloramphenicol acetyltransferase reporter gene functionally demonstrates regions of the promoter containing elements important for transcriptional regulation [23].
• The distribution of glutamine synthetase [L-glutamate: ammonia ligase (ADP-forming), EC 6.3.1.1)] among rat liver parenchymal cells in situ and in primary culture was investigated by indirect immunofluorescence using a specific antiserum [24].

Enzymatic interactions of Glul

• These conditions are also required for the maximal expression of the gamma-glutamyltransferase reaction catalyzed by glutamine synthetase [25].

Regulatory relationships of Glul

• Over similar dose ranges, ET-1 suppressed the glutamine synthetase activity in DBcAMP-treated AC [26].
• Glutamate transport, glutamine synthetase and phosphate-activated glutaminase in rat CNS white matter. A quantitative study [27].
• In contrast, manganese increased glutamine synthetase protein expression and cytokine-stimulated interleukin 6 mRNA expression [28].
• Insulin-like growth factor 1 inhibits glucocorticoid-induced glutamine synthetase activity in cultured L6 rat skeletal muscle cells [29].

Other interactions of Glul

• Surprisingly, hepatocytes do not respond to glucocorticoids with enhanced GS expression, despite the presence of an intact glucocorticoid receptor, which, in the same cells, stimulates expression of other genes such as tyrosine amino transferase [19].
• Astrocytes control synaptic concentration of glutamate via the high affinity glutamate transporters, GLT-1 and GLAST, and the glutamate catabolizing enzyme, glutamine synthetase [30].
• Enzymatic markers of nerve cell development were measured (enolase isoenzymes and glutamine synthetase) [31].
• We found that the intertubular Leydig cells, adjacent to microvessels, express the astrocyte markers: glial fibrillary acidic protein, glutamine synthetase, and S-100 protein [32].
• The zonal distribution of messenger RNAs of alcohol dehydrogenase (little zonation), glutamine synthetase (perivenous) and cytochrome P-450 2E1 (perivenous) messenger RNAs, as analyzed by this technique, were found to be similar to the distribution of corresponding apoproteins [33].

Analytical, diagnostic and therapeutic context of Glul

• We have also cloned and mapped the gene coding for rat glutamine synthetase, and identified, by sequence analysis, areas potentially important for the regulation of glutamine synthetase transcription [23].
• Immunodiffusion and immunoelectrophoretic tests show that rat liver GS and HTC cell GS are immunologically similar but not identical [9].
• In situ hybridization revealed that all pancreatic hepatocytes contain GS and CPS-I mRNAs [34].
• Unlike liver, GS and CPS-I are detected by immunofluorescence in all pancreatic hepatocytes [34].
• Glutamine synthetase shows a striking heterogeneous distribution in normal rat liver as consistently revealed by immunohistochemistry using a specific antiserum against the rat liver enzyme or a cross-reacting antiserum [35].

References