Disease relevance of Glul

• The activity and protein amounts of GS remain normal in wobbler spinal cord although astrocytosis develops [1].
• On the other hand, the concentration of glutamine synthetase remained constant in brain throughout the scrapie disease [2].
• Developmental study of hepatic glutamine synthetase in a mouse model of congenital hyperammonemia [3].
• The sequence was inserted into a eukaryotic expression vector containing the human cytomegalovirus promoter and the glutamine synthetase selection marker, and used to transfect Chinese hamster ovary cells [4].
• Protein kinase Cdelta (PKCdelta) inhibits proliferation and decreases expression of the differentiation marker glutamine synthetase (GS) in C6 glioma cells [5].

Psychiatry related information on Glul

• The effect of intracerebroventricular (i.c.v.) injection of antibodies directed against alpha subunits of Gi, Gx/z, GO and GS regulatory proteins on morphine dependence was analyzed in mice [6].

High impact information on Glul

• Antisense oligodeoxynucleotides to GS protein alpha-subunit sequence accelerate differentiation of fibroblasts to adipocytes [7].
• However, TR-betaGS/GS mutant mice maintained normal hearing at certain frequencies and did not display significant outer hair cell loss, in contrast to TR-beta-/- mice [8].
• TGF-beta 2 also inhibited GS in enriched astrocyte cultures with an ED50 of 10 pg/ml [9].
• In the present in vitro study, we investigated the effects of cytokines on astrocyte glutamine synthetase (GS) activity and subsequently on N-methyl-D-aspartate (NMDA) receptor-mediated neurotoxicity [9].
• The SAMP8 mouse exhibited a decrease in the relevant EPR parameter consistent with oxidative stress (P < 0.002), a decreased glutamine synthetase activity (P < 0.05), and an increased protein carbonyl content (P < 0.01) compared with these parameters in the SAMR1 mouse [10].

Chemical compound and disease context of Glul

• Protection Elicited by Two Glutamine Auxotrophs of Mycobacterium tuberculosis and In Vivo Growth Phenotypes of the Four Unique Glutamine Synthetase Mutants in a Murine Model [11].

Biological context of Glul

• On confluent differentiated cells LPS induced an inhibition of cell proliferation which was associated with a down-regulation of GFAP-mRNA, GS-mRNA and GS expressions and with a transitory increase in IL-1 beta mRNA expression [12].
• In addition, enzyme activity assays demonstrated that oxidation was associated with decreased GS activity, while the activity of lactate dehydrogenase was unchanged in spite of an up-regulation of LDH2 levels [13].
• The decrease of GS mRNA in the spf/Y mice from 28 to 112 days of age (3.72 +/- 0.25 vs 1.68 +/- 0.32, p < 0.01) suggests translational and post-translational modifications in the regulation of GS activity [3].
• It lacks introns, it contains a short poly(A) tract at its 3' end; it is flanked by 10-base pair (bp) direct repeats; and it corresponds closely at its 5' end to the transcription start site of the intron-containing GS gene (GSi) (Kuo, C. F. & Darnell, J. E., Jr. (1989) J. Mol. Biol. 208, 45-56) [14].
• We conclude that the intronless murine GS gene isolated from 3T3-L1 cells arose as a retroposon that was inserted into the genome downstream of a potentially active promoter [14].

Anatomical context of Glul

• Identification by microarray analysis of aspartate aminotransferase and glutamine synthetase as glucocorticoid target genes in a mouse Schwann cell line [15].
• Glutamine synthetase (GS) activity was also detected in the hepatic mitochondria of both specimens [16].
• In this study passages 20-24 were considered "early" and passages 73-90 were considered "late." Activities of glutamine synthetase (GS) and cyclic nucleotide phosphohydrolase (CNP) were used as biochemical markers for astrocytes and oligodendrocytes, respectively [17].
• We report that early-passage C6 glial cells continue to be bipotential cells and when grown in the absence of serum express high GS and CNP activities correlating with the high number of GFAP- and GalC-positive cells, respectively [17].
• Glial cell processes, immunostained for CA or GS, surrounded blood vessels and unstained neurons in the normal gray matter [18].

Associations of Glul with chemical compounds

• Furthermore, there was an increase in the hepatic ornithine-urea cycle (OUC) capacity, with significant increases in the activities of CPS III (3.8-fold), argininosuccinate synthetase + lyase (1.8-fold) and, more importantly, glutamine synthetase (2.2-fold) [19].
• We observed that GS increased during brain maturation in vivo and in vitro, and that addition of hydrocortisone (1 microM, 48 h) to the culture medium induced varying GS activity depending on the developmental stage and the area [20].
• They do not contain GS as do glial cells involved in GABA metabolism, and when they contain protein S100 (rabbit, mouse), its rate is low in comparison to classical glial or ependymal cells [21].
• Complementary expression of glutamine synthetase and carbamoylphosphate synthetase I in ornithine carbamoyltransferase-deficient mouse liver (spf-ash mouse) [22].
• Baicalein treatment also downregulated tumor necrosis factor receptor (TNFRp55) and upregulated noninducible nitric oxide synthase (nNOS) and glutamine synthase (GS) [23].

Regulatory relationships of Glul

• The results of this study indicated that increased accumulation of GFAP mRNA was significant component of reactive gliosis and that the mechanisms responsible for the induction of GFAP were dissociated from those that regulate GS expression [24].
• In contrast, no significant difference in GS mRNA content was detected between control and jimpy brain tissue [24].
• Reduction and expansion of the glutamine synthetase expressing zone in livers from tetracycline controlled TGF-beta1 transgenic mice and multiple starved mice [25].
• For cultures grown in serum-containing medium lacking dibutyryl-cAMP, evidence was obtained that glutamine synthetase was induced by dexamethasone only in part of all cells staining for fibronectin [26].
• Interleukin-1 beta and tumor necrosis factor-alpha suppress dexamethasone induction of glutamine synthetase in primary mouse astrocytes [27].

Other interactions of Glul

• Urea synthesis in the African lungfish Protopterus dolloi--hepatic carbamoyl phosphate synthetase III and glutamine synthetase are upregulated by 6 days of aerial exposure [19].
• Treatment with T3 caused a decrease of GFAP and of its encoding message level in both areas, suggesting a transcriptional regulation of its expression, whereas it had no apparent effect on GS expression [28].
• However, the induction of chondroitin sulfate proteoglycans, tenascin, S-100B as well as glutamate transporter proteins, GLAST and GLT-1, and glutamine synthetase are independent of IL-1RI signaling [29].
• Developmental expression of glial fibrillary acidic protein and glutamine synthetase mRNAs in normal and jimpy mice [24].
• In contrast, the immunoreactivity of glutamine synthetase, another glia-expressed protein, was similar in hippocampal cultures of trisomy 16 mouse and euploid littermates [30].

Analytical, diagnostic and therapeutic context of Glul

• Based on Southern blotting analysis, a single GS gene gives rise to the tissue-specific patterns of GS mRNA expression [31].
• CAT and GS mRNA expression were compared in liver, epididymis, lung, adipocytes, testis, kidney, skeletal muscle and gastrointestinal tract, both quantitatively by ribonuclease-protection analysis and topographically by in situ hybridization [32].
• METHODS: GS was localised immunohistochemically and quantified by real-time RT-PCR and enzymatic activity measurement [25].
• EXPERIMENTAL DESIGN: Heterogeneous expression of glutamine synthetase was examined in detail during mouse liver development by immunohistochemistry and by in situ hybridization [33].
• One-quarter of the offspring expressed the same phenotypic mutation as true wobbler and were detectable by PCR, as they are homozygous for the wobbler-linked Glns allele [34].

References