ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2022
Metabolic Rewiring of Kynurenine Pathway during Hepatic Ischemia-Reperfusion Injury Exacerbates Liver Damage by Impairing NAD Homeostasis.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
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Who cites it
23 citing papers in PubMed, 36 citations in OpenAlex.
- Contactin-2 mitigates heart failure and cardiac remodeling via regulation of NUPR1 and ferroptosis.Biology direct · 2026Article
- Effects and Mechanisms of NAD + on Lung Injury After Cardiac Arrest and Cardiopulmonary Resuscitation in Swine.Shock (Augusta, Ga.) · 2026Article
- Receptor-Mitochondria Crosstalk in the Kynurenine Metabolic Pathway: Integrating Metabolomics and Clinical Mass Spectrometry.Antioxidants (Basel, Switzerland) · 2026Review
- Glutamine metabolism and its roles in tumor radiotherapy by regulating DNA damage repair.Frontiers in cell and developmental biology · 2026Review
- Disruption of Gut Microbiota-Mediated De Novo NADAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Nicotinic acid protects against hepatic ischemia-reperfusion injury via suppressing mitochondrial damage-induced ferroptosis.Liver research (Beijing, China) · 2025Article
- The Role of Mitochondrial Complexes in Liver Diseases.Journal of clinical and translational hepatology · 2025Review
- NAMPT modulates muscle fiber type transition in PAD myopathy via the cGMP-PKG signaling pathway.Biology direct · 2025Article
- Kynurenine-mediated redox regulation provides neuroprotection in central retinal artery occlusion.Journal of translational medicine · 2025Article
- Period3 modulates the NADJournal of advanced research · 2025Article
- NADProgress in orthodontics · 2025Article
- Myeloid but not hepatocytic CD38 is a key driver for hepatic ischemia/reperfusion injury.Signal transduction and targeted therapy · 2025Article
- Acteoside ameliorates hepatocyte ferroptosis and hepatic ischemia-reperfusion injuryActa pharmaceutica Sinica. B · 2025Article
- Multi-time point transcriptomics and metabolomics reveal key transcription and metabolic features of hepatic ischemia-reperfusion injury in mice.Genes & diseases · 2025Article
- Chenodeoxycholic acid modulates cholestatic niche through FXR/Myc/P-selectin axis in liver endothelial cells.Nature communications · 2025Article
- MAPK13 phosphorylates PHGDH and promotes its degradation via chaperone-mediated autophagy during liver injury.Cell discovery · 2025Article
- Role of Kynurenine and Its Derivatives in Liver Diseases: Recent Advances and Future Clinical Perspectives.International journal of molecular sciences · 2025Review
- DL-Tryptophan Alleviates Sepsis-Related Acute Liver Injury via AhR Activation.Journal of inflammation research · 2025Article
- Molecular mechanisms and therapeutic significance of Tryptophan Metabolism and signaling in cancer.Molecular cancer · 2024Review
- Alleviating Recombinant Tissue Plasminogen Activator-induced Hemorrhagic Transformation in Ischemic Stroke via Targeted Delivery of a Ferroptosis Inhibitor.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
Hepatic ischemia-reperfusion (IR) injury remains a common issue lacking effective strategy and validated pharmacological targets. Here, using an unbiased metabolomics screen, this study finds that following murine hepatic IR, liver 3-hydroxyanthranilic acid (3-HAA) and quinolinic acid (QA) decline while kynurenine and kynurenic acid (KYNA) increase. Kynurenine aminotransferases 2, functioning at the key branching point of the kynurenine pathway (KP), is markedly upregulated in hepatocytes during ischemia, shifting the kynurenine metabolic route from 3-HAA and QA to KYNA synthesis. Defects in QA synthesis impair de novo nicotinamide adenine dinucleotide (NAD) biosynthesis, rendering the hepatocytes relying on the salvage pathway for maintenance of NAD and cellular antioxidant defense. Blocking the salvage pathway following IR by the nicotinamide phosphoribosyltransferase inhibitor FK866 exacerbates liver oxidative damage and enhanced IR susceptibility, which can be rescued by the lipid peroxidation inhibitor Liproxstatin-1. Notably, nicotinamide mononucleotide administration once following IR effectively boosts NAD and attenuated IR-induced oxidative stress, inflammation, and cell death in the murine model. Collectively, the findings reveal that metabolic rewiring of the KP partitions it away from NAD synthesis in hepatic IR pathophysiology, and provide proof of concept that NAD augmentation is a promising therapeutic measure for IR-induced liver injury.
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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.