ArticleThe Journal of biological chemistry2006
Tumor necrosis factor-induced toxic liver injury results from JNK2-dependent activation of caspase-8 and the mitochondrial death pathway.
Article in The Journal of biological chemistry, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 97 papers.
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Who cites it
97 citing papers in PubMed, 205 citations in OpenAlex.
- The Role of Novel Immunomodulators in the Treatment of Autoimmune Hepatitis.Journal of clinical and translational hepatology · 2025Review
- Role of C-Jun N-Terminal Kinases on a Stressed Epithelium: Time for Testing Isoform Specificity.Biology · 2025Review
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- Deletion or inhibition of SphK1 mitigates fulminant hepatic failure by suppressing TNFα-dependent inflammation and apoptosis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- ADAM Metalloproteinase Domain 17 Regulates Cholestasis-Associated Liver Injury and Sickness Behavior Development in Mice.Frontiers in immunology · 2021Article
- BRG1 Links TLR4 Trans-Activation to LPS-Induced SREBP1a Expression and Liver Injury.Frontiers in cell and developmental biology · 2021Article
- Huganbuzure Granule Attenuates Concanavalin-A-Induced Immune Liver Injury in Mice via Regulating the Balance of Th1/Th2/Th17/Treg Cells and Inhibiting Apoptosis.Evidence-based complementary and alternative medicine : eCAM · 2021Article
- Si-Wu-Tang Alleviates Nonalcoholic Fatty Liver Disease via Blocking TLR4-JNK and Caspase-8-GSDMD Signaling Pathways.Evidence-based complementary and alternative medicine : eCAM · 2020Article
- Stathmin 1 Induces Murine Hepatocyte Proliferation and Increased Liver Mass.Hepatology communications · 2020Article
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- Curcumin Ameliorates Lead-Induced Hepatotoxicity by Suppressing Oxidative Stress and Inflammation, and Modulating Akt/GSK-3β Signaling Pathway.Biomolecules · 2019Article
- Pterostilbene reverses palmitic acid mediated insulin resistance in HepG2 cells by reducing oxidative stress and triglyceride accumulation.Free radical research · 2019Article
- Delayed Treatment With 4-Methylpyrazole Protects Against Acetaminophen Hepatotoxicity in Mice by Inhibition of c-Jun n-Terminal Kinase.Toxicological sciences : an official journal of the Society of Toxicology · 2019Article
- Decreased Macrophage Autophagy Promotes Liver Injury and Inflammation from Alcohol.Alcoholism, clinical and experimental research · 2019Article
- Cytochrome P450s and Alcoholic Liver Disease.Current pharmaceutical design · 2018Review
- Pentamidine blocks hepatotoxic injury in mice.Hepatology (Baltimore, Md.) · 2017Article
- A novel scoring system based on common laboratory tests predicts the efficacy of TNF-inhibitor and IL-6 targeted therapy in patients with rheumatoid arthritis: a retrospective, multicenter observational study.Arthritis research & therapy · 2017Observational
- Voluntary distance running prevents TNF-mediated liver injury in mice through alterations of the intrahepatic immune milieu.Cell death & disease · 2017Article
- FK866 attenuates acute hepatic failure through c-jun-N-terminal kinase (JNK)-dependent autophagy.Scientific reports · 2017Article
37 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
In vitro studies of hepatocytes have implicated over-activation of c-Jun N-terminal kinase (JNK) signaling as a mechanism of tumor necrosis factor-alpha (TNF)-induced apoptosis. However, the functional significance of JNK activation and the role of specific JNK isoforms in TNF-induced hepatic apoptosis in vivo remain unclear. JNK1 and JNK2 function was, therefore, investigated in the TNF-dependent, galactosamine/lipopolysaccharide (GalN/LPS) model of liver injury. The toxin GalN converted LPS-induced JNK signaling from a transient to prolonged activation. Liver injury and mortality from GalN/LPS was equivalent in wild-type and jnk1-/- mice but markedly decreased in jnk2-/- mice. This effect was not secondary to down-regulation of TNF receptor 1 expression or TNF production. In the absence of jnk2, the caspase-dependent, TNF death pathway was blocked, as reflected by the failure of caspase-3 and -7 and poly(ADP-ribose) polymerase cleavage to occur. JNK2 was critical for activation of the mitochondrial death pathway, as in jnk2-/- mice Bid cleavage and mitochondrial translocation and cytochrome c release were markedly decreased. This effect was secondary to the failure of jnk2-/- mice to activate caspase-8. Liver injury and caspase activation were similarly decreased in jnk2 null mice after GalN/TNF treatment. Ablation of jnk2 did not inhibit GalN/LPS-induced c-Jun kinase activity, although activity was completely blocked in jnk1-/- mice. Toxic liver injury is, therefore, associated with JNK over-activation and mediated by JNK2 promotion of caspase-8 activation and the TNF mitochondrial death pathway through a mechanism independent of c-Jun kinase activity.
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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.