Heterogeneous distribution of glutamine synthetase among rat liver parenchymal cells in situ and in primary culture.
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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. In intact liver, the enzyme was found to be localized exclusively within a very small population of the parenchymal cells surrounding the terminal hepatic venules. Other parts of the parenchyma including non-parenchymal cell types did not stain for this enzyme. Heterogeneity was preserved during isolation of liver parenchymal cells and persisted in cultured cells for at least 3 days. Despite alterations in enzyme activity due to the adaptation of the cells to the culture conditions or due to the hormonal stimulation of the enzyme activity, no change in the relative number of cells expressing this enzyme could be detected. This rather peculiar localization of glutamine synthetase demonstrates an interesting aspect of liver zonation and might have important implications for liver glutamine and, more generally, nitrogen metabolism. Furthermore, it raises the question of whether there might be a phenotypic difference among liver parenchymal cells.
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Ectopic Ctnnb1 activation by itself induces glutamine synthetase (Glul/GS) expression outside the endogenous GS expression normally observed in a two- to three-cell ring of hepatocytes around the central vein.
“In the liver, ectopic Ctnnb1 activation by itself induces glutamine synthetase (gene: Glul; protein: GS) expression outside of the endogenous GS expression normally observed in a two- to three-cell ring of hepatocytes around the central vein (CV) (28–32).”
From The origin of hepatocellular carcinoma depends on metabolic zonation (2026) · cites this paper as [28]
The Results (page unavailable) report that GS-positive rat liver cells form a narrow zone, usually 1–3 cell layers, directly around terminal hepatic venules. The paper does not address ectopic Ctnnb1 activation or show that it induces GS expression outside that zone. (LLM, conf=0.90)
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- Lung,P. and Watford,M. (1976) in Grisolia,S., Baguena,R. and Mayor,F. (eds.), The Urea Cycle, Academic Press, NY, pp. 479488.
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- Authors
- Gebhardt, R., & Mecke, D.
- Venue
- The EMBO Journal
- Published
- 1983-04-01
- Volume
- 2
- Issue
- 4
- Pages
- 567-570
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC555062
- OpenAlex
- W1785497696
- Cited by
- 377
- References
- 0
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 4 · 2023: 1 · 2022: 7 · 2021: 7 · 2020: 10 · 2019: 5 · 2018: 4 · 2017: 3 · 2016: 9 · 2015: 6 · 2014: 10 · 2013: 6 · 2012: 7
- FWCI
- 5.22
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The EMBO Journal (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Deutsche Forschungsgemeinschaft
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Molecular Research
- Keywords
- glutamine synthetase, liver parenchymal cells, enzyme heterogeneity, hepatic zonation, liver zonation, nitrogen metabolism, glutamine metabolism, primary hepatocyte culture, rat liver
- MeSH terms
- Ammonia, Animals, Cells, Cultured, Fluorescent Antibody Technique, Glutamate-Ammonia Ligase, Hepatic Veins, Liver, Male, Rats, Inbred Strains, Rats
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