ArticleHepatology (Baltimore, Md.)2020
c-Jun NH
Article in Hepatology (Baltimore, Md.), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 1 of them a synthesis that pooled it.
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Who cites it
42 citing papers in PubMed, 1 synthesis or guideline pooled it, 78 citations in OpenAlex.
- The pharmacological properties and corresponding mechanisms of farrerol: a comprehensive review.Pharmaceutical biology · 2022Pooled it
- Fused Azine Derivatives Mitigate Long-Term Paracetamol-Induced Liver Fibrosis in Mice: Role of JNK1/ASK1 and Nrf2/HO-1 Signaling Pathways.Inflammation · 2026Article
- Hepatic p38γ exacerbates acetaminophen‑induced acute liver injury via PI3K/Akt‑dependent mechanisms.International journal of molecular medicine · 2026Article
- IRE1/p‑JNK/NRF2 axis-mediated GPX4 upregulation underlies ferroptosis resistance in rheumatoid arthritis fibroblast-like synoviocytes.Arthritis research & therapy · 2026Article
- Combined Manganese-Iron Exposure Reduced Oxidative Stress is Associated with the NRF2/NQO1 Pathway in Astrocytic C8-D1A Cells.Biological trace element research · 2026Article
- Targeting polyamine metabolism and ferroptosis enhances the efficacy of KRAS-targeted therapy depending on KEAP1 status.Nature communications · 2025Article
- Forsythiaside A Reduces Acetaminophen Hepatotoxic Metabolism by Inhibiting Pregnane X Receptor.Molecules (Basel, Switzerland) · 2025Article
- Dysregulation of the JNK signaling pathway in tuberculosis: mechanisms and therapeutic strategies.Frontiers in cellular and infection microbiology · 2025Review
- Age and duration of obesity modulate the inflammatory response and expression of neuroprotective factors in mammalian female brain.Aging cell · 2024Article
- The regulation and function of Nrf2 signaling in ferroptosis-activated cancer therapy.Acta pharmacologica Sinica · 2024Review
- AIBP protects drug-induced liver injury by inhibiting MAPK-mediated NR4A1 expression.iScience · 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
- The Crosstalk between Autophagy and Nrf2 Signaling in Cancer: from Biology to Clinical Applications.International journal of biological sciences · 2024Review
- Targeting Nrf2 signaling in dry eye.International journal of ophthalmology · 2024Review
- Hepatocyte-specific deletion of small heterodimer partner protects mice against acetaminophen-induced hepatotoxicity via activation of Nrf2.Toxicological sciences : an official journal of the Society of Toxicology · 2023Article
- Natural Products for Acetaminophen-Induced Acute Liver Injury: A Review.Molecules (Basel, Switzerland) · 2023Review
- NRF2 has a splicing regulatory function involving the survival of motor neuron (SMN) in non-small cell lung cancer.Oncogene · 2023Article
- How to deal with frenemy NRF2: Targeting NRF2 for chemoprevention and cancer therapy.Journal of food and drug analysis · 2023Review
- USP25 regulates KEAP1-NRF2 anti-oxidation axis and its inactivation protects acetaminophen-induced liver injury in male mice.Nature communications · 2023Article
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
aimsAcetaminophen (APAP) overdose induces severe liver injury and hepatic failure. While the activation of c-Jun NH APPROACH AND
resultsIn this study, we demonstrated that the activation of JNK in mouse liver following exposure to APAP was correlated with the phosphorylation of Nrf2 and down-regulation of the antioxidant response element (ARE)-driven genes, NAD(P)H:quinone dehydrogenase 1, glutathione S-transferase α3, glutathione S-transferase M1, glutathione S-transferase M5, and aldo-keto reductase 1C. The JNK inhibitor, SP600125, or knockdown of JNK by infection of adenovirus expressing JNK small interfering RNA, ameliorated the APAP induced liver toxicity, and inhibited the phosphorylation of Nrf2 and down-regulation of detoxifying enzymes by stabilizing the transcription factor. Mechanistically, JNK antagonized Nrf2- and ARE-driven gene expression in a Kelch-like ECH-associated protein 1-independent manner. Biochemical analysis revealed that phosphorylated JNK (P-JNK) directly interacted with the Nrf2-ECH homology (Neh) 1 domain of Nrf2 and phosphorylated the serine-aspartate-serine motif 1 (SDS1) region in the Neh6 domain of Nrf2.
conclusionsMass spectrometric analysis identified serine 335 in the SDS1 region of mNrf2 as the major phosphorylation site for modulation of Nrf2 ubiquitylation by P-JNK. This study demonstrates that Nrf2 is a target of P-JNK in AILI. Our finding may provide a strategy for the treatment of AILI.
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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.