ArticleProceedings of the National Academy of Sciences of the United States of America2014
TRPM2 channels mediate acetaminophen-induced liver damage.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 98 citations in OpenAlex.
- Article
- Membrane-Targeted Consequences of Acetaminophen Toxicity and Off-Target Effects of Antimicrobial Peptides on Host Cell Membranes.International journal of molecular sciences · 2026Review
- The potential of curcumin in mitigating acetaminophen-induced liver damage.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Honeysuckle-Derived Exosome-Like Nanovesicles Protect Against Acute Liver Failure by Modulating Gut Microbiota.International journal of nanomedicine · 2025Article
- Selectively targeting the AdipoR2-CaM-CaMKII-NOS3 axis by SCM-198 as a rapid-acting therapy for advanced acute liver failure.Nature communications · 2024Article
- TLR4 induced TRPM2 mediated neuropathic pain.Frontiers in pharmacology · 2024Review
- Bidirectional regulation mechanism of TRPM2 channel: role in oxidative stress, inflammation and ischemia-reperfusion injury.Frontiers in immunology · 2024Review
- Potassium channels as novel molecular targets in hepatocellular carcinoma (Review).Oncology reports · 2023Review
- TRP (transient receptor potential) ion channel family: structures, biological functions and therapeutic interventions for diseases.Signal transduction and targeted therapy · 2023Review
- TRPM2-mediated CaCell communication and signaling : CCS · 2023Review
- The molecular mechanisms of acetaminophen-induced hepatotoxicity and its potential therapeutic targets.Experimental biology and medicine (Maywood, N.J.) · 2023Review
- Endoplasmic Reticulum Stress and Mitochondrial Stress in Drug-Induced Liver Injury.Molecules (Basel, Switzerland) · 2023Review
- Expression and functions of transient receptor potential channels in liver diseases.Acta pharmaceutica Sinica. B · 2023Review
- Cell death induction and protection by activation of ubiquitously expressed anion/cation channels. Part 3: the roles and properties of TRPM2 and TRPM7.Frontiers in cell and developmental biology · 2023Review
- TRPM2 protects against cisplatin-induced acute kidney injury and mitochondrial dysfunction via modulating autophagy.Theranostics · 2023Article
- Role of CaInternational journal of molecular medicine · 2022Review
- Influence of Acetaminophen on Molecular Adsorption and Transport Properties at Colloidal Liposome Surfaces Studied by Second Harmonic Generation Spectroscopy.Langmuir : the ACS journal of surfaces and colloids · 2022Article
- Hyperthermia and Serotonin: The Quest for a "Better Cyproheptadine".International journal of molecular sciences · 2022Review
- TRPM2 Non-Selective Cation Channels in Liver Injury Mediated by Reactive Oxygen Species.Antioxidants (Basel, Switzerland) · 2021Review
- Drug-Induced Liver Injury: Clinical Evidence of N-Acetyl Cysteine Protective Effects.Oxidative medicine and cellular longevity · 2021Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Acetaminophen (paracetamol) is the most frequently used analgesic and antipyretic drug available over the counter. At the same time, acetaminophen overdose is the most common cause of acute liver failure and the leading cause of chronic liver damage requiring liver transplantation in developed countries. Acetaminophen overdose causes a multitude of interrelated biochemical reactions in hepatocytes including the formation of reactive oxygen species, deregulation of Ca(2+) homeostasis, covalent modification and oxidation of proteins, lipid peroxidation, and DNA fragmentation. Although an increase in intracellular Ca(2+) concentration in hepatocytes is a known consequence of acetaminophen overdose, its importance in acetaminophen-induced liver toxicity is not well understood, primarily due to lack of knowledge about the source of the Ca(2+) rise. Here we report that the channel responsible for Ca(2+) entry in hepatocytes in acetaminophen overdose is the Transient Receptor Potential Melanostatine 2 (TRPM2) cation channel. We show by whole-cell patch clamping that treatment of hepatocytes with acetaminophen results in activation of a cation current similar to that activated by H2O2 or the intracellular application of ADP ribose. siRNA-mediated knockdown of TRPM2 in hepatocytes inhibits activation of the current by either acetaminophen or H2O2. In TRPM2 knockout mice, acetaminophen-induced liver damage, assessed by the blood concentration of liver enzymes and liver histology, is significantly diminished compared with wild-type mice. The presented data strongly suggest that TRPM2 channels are essential in the mechanism of acetaminophen-induced hepatocellular death.
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