ArticleCell death & disease2018
Poly(ADP-ribosyl)ated PXR is a critical regulator of acetaminophen-induced hepatotoxicity.
Article in Cell death & disease, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
22 citing papers in PubMed, 31 citations in OpenAlex.
- PXR ribosylation at E194 amplifies NAPQI in acetaminophen‒induced liver injury in mice, rescued by Schisandrin B.Acta pharmacologica Sinica · 2026Article
- Pregnane X receptor (NR1I2) deficiency in mice reveals context-dependent regulation of inflammatory homeostasis.Frontiers in immunology · 2026Review
- SRY mediates male-specific susceptibility to acute liver injury.Cell communication and signaling : CCS · 2025Article
- Sesamin alleviates drug-induced hepatotoxicity via autophagy enhancement and ferroptosis inhibition.Redox report : communications in free radical research · 2025Article
- PARP‑1 in liver diseases: Molecular mechanisms, therapeutic potential and emerging clinical applications (Review).Molecular medicine reports · 2025Review
- Unveiling hepatic Krüppel-like factor 15 as the key regulator of cyclosporine A metabolism and adverse effects.Drug metabolism and disposition: the biological fate of chemicals · 2025Article
- Forsythiaside A Reduces Acetaminophen Hepatotoxic Metabolism by Inhibiting Pregnane X Receptor.Molecules (Basel, Switzerland) · 2025Article
- Hepatic Sirt6 activation abrogates acute liver failure.Cell death & disease · 2024Article
- S-nitrosylation attenuates pregnane X receptor hyperactivity and acetaminophen-induced liver injury.JCI insight · 2024Article
- PARP1 Promotes Heart Regeneration and Cardiomyocyte Proliferation.International journal of biological sciences · 2024Article
- Article
- The role of pregnane X receptor (PXR) in substance metabolism.Frontiers in endocrinology · 2022Review
- Review
- FUNDC1-dependent mitochondria-associated endoplasmic reticulum membranes are involved in angiogenesis and neoangiogenesis.Nature communications · 2021Article
- CTRP13 Mitigates Abdominal Aortic Aneurysm Formation via NAMPT1.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Article
- E3 Ligase FBXW2 Is a New Therapeutic Target in Obesity and Atherosclerosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2020Article
- PXR-mediated idiosyncratic drug-induced liver injury: mechanistic insights and targeting approaches.Expert opinion on drug metabolism & toxicology · 2020Review
- PXR: a center of transcriptional regulation in cancer.Acta pharmaceutica Sinica. B · 2020Review
- Endothelial FAM3A positively regulates post-ischaemic angiogenesis.EBioMedicine · 2019Article
- Poly(ADP-ribose) polymerase 1 accelerates vascular calcification by upregulating Runx2.Nature communications · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Acetaminophen (APAP) overdose is the most frequent cause of acute liver failure and remains a critical problem in medicine. PARP1-dependent poly(ADPribosyl)ation is a key mediator of cellular stress responses and functions in multiple physiological and pathological processes. However, whether it is involved in the process of APAP metabolism remains elusive. In this study, we find that PARP1 is activated in mouse livers after APAP overdose. Pharmacological or genetic manipulations of PARP1 are sufficient to suppress the APAP-induced hepatic toxicity and injury, as well as reduced APAP metabolism. Mechanistically, we identify pregnane X receptor (PXR) as a substrate of PARP1-mediated poly(ADP-ribosyl)ation. The poly(ADP-ribosyl)ation of PXR in ligand-binding domain activates PXR competitively and solidly, facilitates its recruitment to target gene CYP3A11 promoter, and promotes CYP3A11 gene transcription, thus resulting in increases of APAP pro-toxic metabolism. Additionally, PXR silence antagonizes the effects of PARP1 on APAP-induced hepatotoxicity. These results identifies poly(ADP-ribosyl)ation of PXR by PARP1 as a key step in APAP-induced liver injury. We propose that inhibition of PARP1-dependent poly(ADP-ribosyl)ation might represent a novel approach for the treatment of drug-induced hepatotoxicity.
Indexed as
Identifiers
What OpenQuestion holds
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.