ArticleProceedings of the National Academy of Sciences of the United States of America2015
Hyperammonemia in gene-targeted mice lacking functional hepatic glutamine synthetase.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 94 citations in OpenAlex.
- Diammonium phosphate supplementation in low-protein diets improves nitrogen utilization and feed efficiency without impairing carcass traits or meat quality in finishing pigs.Animal nutrition (Zhongguo xu mu shou yi xue hui) · 2026Article
- Haemodynamic control of zonated liver function via instructive vascular Wnt signalling.Nature communications · 2026Article
- Comparative and immunohistochemical analyses on hepatic zonation in vertebrates with a special reference to evolution.Cell and tissue research · 2026Article
- Advances in understanding, diagnosing, and treating hepatic encephalopathy: from epidemiology to emerging therapies.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- 3D reconstruction of human liver tissue at cellular resolution.Science advances · 2026Article
- Impaired nitrogenous waste clearance promotes hepatocellular carcinoma.Science advances · 2026Article
- From metabolism to mood regulation: astrocytes as a driver of depression.Frontiers in cellular neuroscience · 2026Review
- Ammonia reduces glutamine synthetase expression in astrocytes via activation of Hippo-YAP signaling pathways.Communications biology · 2025Article
- Hepatic stellate cells: balancing homeostasis, hepatoprotection and fibrogenesis in health and disease.Nature reviews. Gastroenterology & hepatology · 2025Review
- Novel roles of ammonia in physiology and cancer.Journal of molecular cell biology · 2025Review
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- Ammonia-induced stress response in liver disease progression and hepatic encephalopathy.Nature reviews. Gastroenterology & hepatology · 2024Review
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- Dietary protein load affects the energy and nitrogen balance requiring liver glutamate dehydrogenase to maintain physical activity.The Journal of biological chemistry · 2024Article
- An innate immune response to adeno-associated virus genomes decreases cortical dendritic complexity and disrupts synaptic transmission.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Neuroprotective and cognitive enhancing effects of herbecetin against thioacetamide induced hepatic encephalopathy in rats via upregulation of AMPK and SIRT1 signaling pathways.Scientific reports · 2024Article
- In vitro heterochronic parabiosis identifies pigment epithelium-derived factor as a systemic mediator of rejuvenation by young blood.bioRxiv : the preprint server for biology · 2024Article
- Glutamine metabolism, a double agent combating or fuelling hepatocellular carcinoma.JHEP reports : innovation in hepatology · 2024Review
- Gut-derived ammonia contributes to alcohol-related fatty liver development via facilitating ethanol metabolism and provoking ATF4-dependent de novo lipogenesis activation.Metabolism: clinical and experimental · 2024Article
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Urea cycle defects and acute or chronic liver failure are linked to systemic hyperammonemia and often result in cerebral dysfunction and encephalopathy. Although an important role of the liver in ammonia metabolism is widely accepted, the role of ammonia metabolizing pathways in the liver for maintenance of whole-body ammonia homeostasis in vivo remains ill-defined. Here, we show by generation of liver-specific Gln synthetase (GS)-deficient mice that GS in the liver is critically involved in systemic ammonia homeostasis in vivo. Hepatic deletion of GS triggered systemic hyperammonemia, which was associated with cerebral oxidative stress as indicated by increased levels of oxidized RNA and enhanced protein Tyr nitration. Liver-specific GS-deficient mice showed increased locomotion, impaired fear memory, and a slightly reduced life span. In conclusion, the present observations highlight the importance of hepatic GS for maintenance of ammonia homeostasis and establish the liver-specific GS KO mouse as a model with which to study effects of chronic hyperammonemia.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.