ArticleAmerican journal of physiology. Gastrointestinal and liver physiology2014
Carbamoyl phosphate synthetase-1 is a rapid turnover biomarker in mouse and human acute liver injury.
Article in American journal of physiology. Gastrointestinal and liver physiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
What it found
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The trial behind it
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Who cites it
30 citing papers in PubMed, 45 citations in OpenAlex.
- CPS1: a multipurpose mitochondrial enzyme, bile protein, acute liver injury biomarker, and cytokine.Gut · 2026Review
- Single-Cell Analysis of Hepatic Non-Parenchymal Cells Reveals Endothelial Dysfunction and Altered Endothelial and B Cell Communication in Acute-on-Chronic Liver Failure.Journal of immunology research · 2026Article
- From fructose to the future: liver disease biomarkers and their prognostic value in acute liver failure.Critical reviews in clinical laboratory sciences · 2025Review
- Natural Products That Protect Against Acetaminophen Hepatotoxicity: A Call for Increased Rigor in Preclinical Studies of Dietary Supplements.Journal of dietary supplements · 2025Review
- Discovery of biophysical rate laws from the electronic health record enables real-time liver injury estimation from transaminase dynamics.Cell reports. Medicine · 2024Article
- Spatial Transcriptome Mapping of the Desmoplastic Growth Pattern of Colorectal Liver Metastases by In Situ Sequencing Reveals a Biologically Relevant Zonation of the Desmoplastic Rim.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- Central Mechanisms of Acetaminophen Hepatotoxicity: Mitochondrial Dysfunction by Protein Adducts and Oxidant Stress.Drug metabolism and disposition: the biological fate of chemicals · 2024Review
- The Role of Mechanistic Biomarkers in Understanding Acetaminophen Hepatotoxicity in Humans.Drug metabolism and disposition: the biological fate of chemicals · 2024Review
- Associations between Chronic Kidney Disease and Migraine Incidence: Findings from a Korean Longitudinal Big Data Study.Journal of personalized medicine · 2024Article
- Article
- The Role of Carbamoyl Phosphate Synthetase 1 as a Prognostic Biomarker in Patients With Acetaminophen-induced Acute Liver Failure.Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association · 2023Article
- Hypoosmosis alters hepatocyte mitochondrial morphology and induces selective release of carbamoyl phosphate synthetase 1.American journal of physiology. Gastrointestinal and liver physiology · 2023Article
- Identification of flucloxacillin-modified hepatocellular proteins: implications in flucloxacillin-induced liver injury.Toxicological sciences : an official journal of the Society of Toxicology · 2023Article
- Tandem mass tag-based quantitative proteomic profiling identifies candidate serum biomarkers of drug-induced liver injury in humans.Nature communications · 2023Article
- Redox Activation of Mitochondrial DAMPs and the Metabolic Consequences for Development of Autoimmunity.Antioxidants & redox signaling · 2022Review
- Article
- Acetaminophen Hepatotoxicity.Seminars in liver disease · 2019Article
- Constitutive release of CPS1 in bile and its role as a protective cytokine during acute liver injury.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- HMGB1 is a Central Driver of Dynamic Pro-inflammatory Networks in Pediatric Acute Liver Failure induced by Acetaminophen.Scientific reports · 2019Article
- Leukocyte cell derived chemotaxin-2 (Lect2) as a predictor of survival in adult acute liver failure.Translational gastroenterology and hepatology · 2019Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Several serum markers are used to assess hepatocyte damage, but they have limitations related to etiology specificity and prognostication. Identification of novel hepatocyte-specific biomarkers could provide important prognostic information and better pathogenesis classification. We tested the hypothesis that hepatocyte-selective biomarkers are released after subjecting isolated mouse hepatocytes to Fas-ligand-mediated apoptosis. Proteomic analysis of hepatocyte culture medium identified the mitochondrial matrix protein carbamoyl phosphate synthetase-1 (CPS1) among the most readily detected proteins that are released by apoptotic hepatocytes. CPS1 was also detected in mouse serum upon acute challenge with Fas-ligand or acetaminophen and in hepatocytes upon hypoosmotic stress, independent of hepatocyte caspase activation. Furthermore, CPS1 was observed in sera of mice chronically fed the hepatotoxin 3,5-diethoxycarbonyl-1,4-dihydrocollidine. Mouse CPS1 detectability was similar in serum and plasma, and its half-life was 126 ± 9 min. Immune staining showed that CPS1 localized to mouse hepatocytes but not ductal cells. Analysis of a few serum samples from patients with acute liver failure (ALF) due to acetaminophen, Wilson disease, or ischemia showed readily detectable CPS1 that was not observed in several patients with chronic viral hepatitis or in control donors. Notably, CPS1 rapidly decreased to undetectable levels in sera of patients with acetaminophen-related ALF who ultimately recovered, while alanine aminotransferase levels remained elevated. Therefore, CPS1 becomes readily detectable upon hepatocyte apoptotic and necrotic death in culture or in vivo. Its abundance and short serum half-life, compared with alanine aminotransferase, suggest that it may be a useful prognostic biomarker in human and mouse liver injury.
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Registered trials
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.