Cloning and functional characterization of the rat glutamine synthetase gene

Mill, John F.; Mearow, Karen M.; Purohit, Hemant J.; Haleem‐Smith, Hana; King, Ron G.; Freese, Ernst

doi:10.1016/0169-328x(91)90003-g

Cited by 46 publications

(30 citation statements)

References 34 publications

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“…Deficiency of AS may also lead to increased amounts of ammonia and decreased amounts of arginine [53]. An increased expression of glutamine synthetase (FC 2.4, group 13) in the beta cell phenotype was detected, possibly as a compensation for the increased levels of ammonia, since glutamine synthetase is involved in the detoxification of ammonia [54]. Furthermore, it could be speculated that the beta cell phenotype compensates for the low arginine levels by activating several pathways to increase the levels of arginine.…”

Section: Glycolysis and Energy Generationmentioning

confidence: 99%

Gene expression profiles during beta cell maturation and after IL-1? exposure reveal important roles of Pdx-1 and Nkx6.1 for IL-1? sensitivity

et al. 2004

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Aim/hypothesis. Maturation of the beta cells in the islets of Langerhans is dependent upon sequential activation of different transcription factors such as Pdx-1 and Nkx6.1. This maturation is associated with an acquired sensitivity to cytokines and may eventually lead to type 1 diabetes. The aims of this study were to characterise changes in mRNA expression during beta cell maturation as well as after interleukin-1β (IL-1β) exposure. Methods. Transcriptome analyses were performed on two phenotypes characterised as a glucagon-producing pre-beta-cell phenotype (NHI-glu), which matures to an IL-1β-sensitive insulin-producing beta cell phenotype (NHI-ins). Beta cell lines over-expressing Pdx-1 or Nkx6.1, respectively, were used for functional characterisation of acquired IL-1β sensitivity.Results. During beta cell maturation 98 fully annotated mRNAs changed expression levels. Of these, 50 were also changed after 24 h of IL-1β exposure. In addition, 522 and 197 fully annotated mRNAs, not affected by maturation, also changed expression levels following IL-1β exposure of the beta cell and the prebeta-cell phenotype, respectively. Beta cell maturation was associated with an increased expression of Nkx6.1, whereas both Pdx-1 and Nkx6.1 expression were decreased following IL-1β exposure. Over-expression of Nkx6.1 or Pdx-1 in cell lines resulted in a significantly increased sensitivity to IL-1β. Conclusions/interpretation. These results suggest that the final beta cell maturation accompanied by increased IL-1β sensitivity is, in part, dependent upon the expression of genes regulated by Pdx-1 and Nkx6.1. Future classification of the genes regulated by these transcription factors and changed during beta cell maturation should elucidate their role in the acquired sensitivity to IL-1β and may be helpful in identifying new targets for intervention/prevention strategies.

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Section: Glycolysis and Energy Generationmentioning

confidence: 99%

Gene expression profiles during beta cell maturation and after IL-1? exposure reveal important roles of Pdx-1 and Nkx6.1 for IL-1? sensitivity

et al. 2004

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“…The RNA was blotted to nitrocellulose, baked, and hybridized in 5 x SSC/50% formamide at 42°C for 16-18 h with a 32P-labeled rat GS cDNAprobe Mill et al, 1989). The cDNA probe was labeled with 32P-dCTP (Amersham) using a random primers labeling kit (BRL).…”

Section: Rna Isolation and Analysismentioning

confidence: 99%

Neuron–glial interactions involved in the regulation of glutamine synthetase

Mearow¹,

Mill²,

Freese³

1990

Glia

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Cocultures of rat cortical astrocytes with cerebellar granule cell neurons, but not a variety of other cell types tested, resulted in an induction of glutamine synthetase (GS) mRNA over the basal levels expressed in pure astrocyte cultures. This induction involved both contact- and noncontact-mediated events and may be a result of astroglial differentiation promoted by interactions with the primary neurons. Astrocytes grown in the presence of the granule neurons (but not the other cell types tested) exhibited a more complex, process-bearing morphology typical of more differentiated cells. In addition, glial cell proliferation was inhibited not only by the presence of live granule cells, but also by fixed neurons and neuronal membranes. Under the same experimental conditions, GS mRNA was increased (two- to threefold) compared with the expression observed in pure astrocyte cultures. Because of the role of GS in glutamate metabolism and the influence of the glutamatergic granule neurons on glial GS mRNA levels, the effect of exogenous glutamate was examined. The addition of 100 microM glutamate to the culture medium resulted in an increase in GS mRNA in the astrocyte cultures similar to that observed in the cocultures, where the addition of glutamate did not further increase GS mRNA levels. These results provide further evidence for the importance of neuron-glial interactions in the regulation of glial gene expression.

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“…Chinese hamster (32), mouse (40), rat (52,73), and chick (61,82) GS genes have been cloned, and regions of the promoters containing elements important for transcription have been identified (52,73,82). The chick genome contains a single GS gene (59).…”

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confidence: 99%

Involvement of a C/EBP-like protein in the acquisition of responsiveness to glucocorticoid hormones during chick neural retina development.

Ben-Or¹,

Okret²

1993

Mol. Cell. Biol.

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The glucocorticoid receptor in chicken embryonic neural retina is expressed early in ontogeny, yet the tissue's response to the glucocorticoid hormone, i.e., induction of glutamine synthetase (GS), develops later, only during week 2 of ontogeny. Transient transfection of embryonic day 7 (E7) retinal cells, which are nonresponsive to glucocorticoids, with chimeric plasmids containing the chloramphenicol acetyltransferase reporter gene under the control of glucocorticoid-responsive promoters demonstrated that GR in E7 cells is a functional transactivating factor. We show that the limiting transcription factor that controls the developmental acquisition of responsiveness to glucocorticoids is similar to a CCAAT enhancer-binding protein (C/EBP). This protein recognizes a sequence in the promoter of the chick GS gene, which is required for eliciting the glucocorticoid response. Retinal C/EBP-like protein was not detected in the glucocorticoid-nonresponsive (E7) proliferating glioblasts but was found to be present in the glucocorticoid-responsive (E12) postmitotic cells.

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Cloning and functional characterization of the rat glutamine synthetase gene

Cited by 46 publications

References 34 publications

Gene expression profiles during beta cell maturation and after IL-1? exposure reveal important roles of Pdx-1 and Nkx6.1 for IL-1? sensitivity

Gene expression profiles during beta cell maturation and after IL-1? exposure reveal important roles of Pdx-1 and Nkx6.1 for IL-1? sensitivity

Neuron–glial interactions involved in the regulation of glutamine synthetase

Involvement of a C/EBP-like protein in the acquisition of responsiveness to glucocorticoid hormones during chick neural retina development.

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