ArticleThe Journal of clinical investigation2023
Asparagine protects pericentral hepatocytes during acute liver injury.
Article in The Journal of clinical investigation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 27 citations in OpenAlex.
- Phospholipid phosphatase 2 drives liver repair and regeneration after acute liver injury.Signal transduction and targeted therapy · 2026Article
- Identification of biomarkers related to amino acid metabolism in nonobstructive azoospermia by bioinformatics.Medicine · 2026Article
- A Manifold-Based Measure of Transcriptional Entropy for Quantifying Aging in Single Cells.bioRxiv : the preprint server for biology · 2026Article
- Macrophage Plg-RJournal of thrombosis and haemostasis : JTH · 2026Article
- Asparaginase and Autophagy Inhibitors Effectively Remove Senescent Cells by Synergistically Limiting Asparagine Supply.Aging cell · 2025Article
- Glucocorticoids trigger muscle-liver crosstalk to attenuate acute liver injury and promote liver regeneration via the FGF6-FGFBP1 axis.Military Medical Research · 2025Article
- The Study of Approaches to Modeling Oxidative Stress in Male Wistar Rats: The Comparative Analysis of Diet-Induced, Chemically Induced, and Physiologically Induced Models.International journal of molecular sciences · 2025Article
- Kehuang capsule inhibits MAPK and AKT signaling pathways to mitigate CClLiver research (Beijing, China) · 2024Article
- Asparagine Availability Is a Critical Limiting Factor for Infectious Spleen and Kidney Necrosis Virus Replication.Viruses · 2024Article
- Plasma D-asparagine and the D/L-serine ratio reflect chronic kidney diseases in children regardless of physique.Amino acids · 2024Article
- LRH-1 induces hepatoprotective nonessential amino acids in response to acute liver injury.The Journal of clinical investigation · 2023Article
- Nootkatone Supplementation Attenuates Carbon Tetrachloride Exposure-Induced Nephrotoxicity in Mice.Antioxidants (Basel, Switzerland) · 2023Article
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10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The nonessential amino acid asparagine can only be synthesized de novo by the enzymatic activity of asparagine synthetase (ASNS). While ASNS and asparagine have been implicated in the response to numerous metabolic stressors in cultured cells, the in vivo relevance of this enzyme in stress-related pathways remains unexplored. Here, we found ASNS to be expressed in pericentral hepatocytes, a population of hepatic cells specialized in xenobiotic detoxification. ASNS expression was strongly enhanced in 2 models of acute liver injury: carbon tetrachloride (CCl4) and acetaminophen. We found that mice with hepatocyte-specific Asns deletion were more prone to pericentral liver damage than their control littermates after toxin exposure. This phenotype could be reverted by i.v. administration of asparagine. Unexpectedly, the stress-induced upregulation of ASNS involved an ATF4-independent, noncanonical pathway mediated by the nuclear receptor, liver receptor homolog 1 (LRH-1; NR5A2). Altogether, our data indicate that the induction of the asparagine-producing enzyme ASNS acts as an adaptive mechanism to constrain the necrotic wave that follows toxin administration and provide proof of concept that i.v. delivery of asparagine can dampen hepatotoxin-induced pericentral hepatocellular death.
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