ArticleHepatology (Baltimore, Md.)2019
p53 Up-regulated Modulator of Apoptosis Induction Mediates Acetaminophen-Induced Necrosis and Liver Injury in Mice.
Article in Hepatology (Baltimore, Md.), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 83 citations in OpenAlex.
- The Bacterial Metabolite Lndole-3-Propionic Acid Alleviates Acetaminophen-Induced Acute Liver Injury Partly through the Aryl Hydrocarbon Receptor Pathway.Journal of microbiology and biotechnology · 2026Article
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- The pivotal role of mitochondria in the pathogenesis and treatment of liver failure: a comprehensive review.Molecular and cellular biochemistry · 2026Review
- Multi-lineage hepatic organoids reveal toxic exosome mediated indirect hepatotoxicity.Nature communications · 2026Article
- Investigating Mitochondrial Viscosity in Ferroptosis-Mediated Drug-Induced Liver Injury using a Double-Targeted Strategy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The multifaceted role of PUMA in cell death pathways: its therapeutic potential across cancer types.Cell communication and signaling : CCS · 2025Review
- Depletion of oxysterol-binding proteins by OSW-1 triggers RIP1/RIP3-independent necroptosis and sensitization to cancer immunotherapy.Cell death and differentiation · 2025Article
- Developmentally Regulated CYP2E1 Expression Is Associated with a Fetal Pulmonary Transcriptional Response to Maternal Acetaminophen Exposure.Biomedicines · 2025Article
- Nanoscale synthetic biology with innovative medicinal applications.Fundamental research · 2025Review
- Article
- Inhibition RIP1 prevents acute liver failure by suppressing hepatic apoptosis and attenuating the secretion of TNF-α from macrophages.European journal of medical research · 2025Article
- Nimbolide Targeting SIRT1 Protects Against Acetaminophen-Induced Acute Liver Injury by Regulating Oxidative Stress and Endoplasmic Reticulum Stress.Pharmacology research & perspectives · 2025Article
- AIBP protects drug-induced liver injury by inhibiting MAPK-mediated NR4A1 expression.iScience · 2024Article
- Drug-induced oxidative stress actively prevents caspase activation and hepatocyte apoptosis.Cell death & disease · 2024Article
- GPR116 alleviates acetaminophen-induced liver injury in mice by inhibiting endoplasmic reticulum stress.Cellular and molecular life sciences : CMLS · 2024Article
- NLRP3 deficiency protects against acetaminophen‑induced liver injury by inhibiting hepatocyte pyroptosis.Molecular medicine reports · 2024Article
- S-nitrosylation attenuates pregnane X receptor hyperactivity and acetaminophen-induced liver injury.JCI insight · 2024Article
- Non-canonical BIM-regulated energy metabolism determines drug-induced liver necrosis.Cell death and differentiation · 2024Article
- P2rx1 deficiency alleviates acetaminophen-induced acute liver failure by regulating the STING signaling pathway.Cell biology and toxicology · 2023Article
- Natural Products for Acetaminophen-Induced Acute Liver Injury: A Review.Molecules (Basel, Switzerland) · 2023Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Acetaminophen (APAP) overdose is one of the leading causes of hepatotoxicity and acute liver failure in the United States. Accumulating evidence suggests that hepatocyte necrosis plays a critical role in APAP-induced liver injury (AILI). However, the mechanisms of APAP-induced necrosis and liver injury are not fully understood. In this study, we found that p53 up-regulated modulator of apoptosis (PUMA), a B-cell lymphoma-2 (Bcl-2) homology domain 3 (BH3)-only Bcl-2 family member, was markedly induced by APAP in mouse livers and in isolated human and mouse hepatocytes. PUMA deficiency suppressed APAP-induced mitochondrial dysfunction and release of cell death factors from mitochondria, and protected against APAP-induced hepatocyte necrosis and liver injury in mice. PUMA induction by APAP was p53 independent, and required receptor-interacting protein kinase 1 (RIP1) and c-Jun N-terminal kinase (JNK) by transcriptional activation. Furthermore, a small-molecule PUMA inhibitor, administered after APAP treatment, mitigated APAP-induced hepatocyte necrosis and liver injury. Conclusion: Our results demonstrate that RIP1/JNK-dependent PUMA induction mediates AILI by promoting hepatocyte mitochondrial dysfunction and necrosis, and suggest that PUMA inhibition is useful for alleviating acute hepatotoxicity attributed to APAP overdose.
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