ArticleJournal of hepatology2011
Glycogen synthase kinase-3 (GSK-3) inhibition attenuates hepatocyte lipoapoptosis.
Article in Journal of hepatology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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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.
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Who cites it
38 citing papers in PubMed, 84 citations in OpenAlex.
- Killing hepatocellular carcinoma in the NAFLD/NASH stage: a comprehensive perspective on targeting regulated cell death.Cell death discovery · 2025Review
- Inhibition of mitochondrial OMA1 ameliorates osteosarcoma tumorigenesis.Cell death & disease · 2024Article
- Role of Glycogen Synthase Kinase-3 in Interferon-γ-Mediated Immune Hepatitis.International journal of molecular sciences · 2022Review
- Current insights in molecular characterization of non-alcoholic fatty liver disease and treatment.Frontiers in endocrinology · 2022Review
- Stress kinases in the development of liver steatosis and hepatocellular carcinoma.Molecular metabolism · 2021Review
- Peripherally Selective CB1 Receptor Antagonist Improves Symptoms of Metabolic Syndrome in Mice.ACS pharmacology & translational science · 2021Article
- Association of Adipose Tissue and Adipokines with Development of Obesity-Induced Liver Cancer.International journal of molecular sciences · 2021Review
- Protein Phosphatase 4 Promotes Hepatocyte Lipoapoptosis by Regulating RAC1/MLK3/JNK Pathway.Oxidative medicine and cellular longevity · 2021Article
- Combining Auxin-Induced Degradation and RNAi Screening Identifies Novel Genes Involved in Lipid Bilayer Stress Sensing inG3 (Bethesda, Md.) · 2020Article
- Lipid droplet-associated kinase STK25 regulates peroxisomal activity and metabolic stress response in steatotic liver.Journal of lipid research · 2020Article
- GSK3β inhibition suppresses the hepatic lipid accumulation in Schizothorax prenanti.Fish physiology and biochemistry · 2019Article
- The effect of palmitic acid on inflammatory response in macrophages: an overview of molecular mechanisms.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2019Review
- Non-obesogenic doses of fatty acids modulate the functionality of the circadian clock in the liver.Cellular and molecular life sciences : CMLS · 2019Article
- Cold Physical Plasma Modulates p53 and Mitogen-Activated Protein Kinase Signaling in Keratinocytes.Oxidative medicine and cellular longevity · 2019Article
- To die or not to die: death signaling in nonalcoholic fatty liver disease.Journal of gastroenterology · 2018Review
- Apoptosis and non-alcoholic fatty liver diseases.World journal of gastroenterology · 2018Review
- Hepatitis C Virus Infection Increases c-Jun N-Terminal Kinase (JNK) Phosphorylation and Accentuates Hepatocyte Lipoapoptosis.Medical science monitor : international medical journal of experimental and clinical research · 2017Article
- Article
- Glycycoumarin inhibits hepatocyte lipoapoptosis through activation of autophagy and inhibition of ER stress/GSK-3-mediated mitochondrial pathway.Scientific reports · 2016Article
- Biliverdin Reductase A Attenuates Hepatic Steatosis by Inhibition of Glycogen Synthase Kinase (GSK) 3β Phosphorylation of Serine 73 of Peroxisome Proliferator-activated Receptor (PPAR) α.The Journal of biological chemistry · 2016Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
BACKGROUNDS &
aimsSaturated free fatty acids induce hepatocyte lipoapoptosis, a key pathologic feature of non-alcoholic steatohepatitis. The saturated free fatty acid palmitate induces hepatocyte lipoapoptosis via an endoplasmic reticulum stress pathway resulting in c-Jun-N-terminal (JNK) activation. Glycogen synthase kinase (GSK)-3 is a serine/threonine kinase which may also promote JNK activation. Thus, our aim was to determine if GSK-3 inhibition suppresses palmitate induced JNK activation and lipoapoptosis.
methodsFor these studies, we employed mouse primary hepatocytes, Huh-7 and Hep3B cell lines.
resultsPalmitate-induced GSK-3 activation was identified by phosphorylation of its substrate glycogen synthase. GSK-3 pharmacologic inhibition, by GSK-3 inhibitor IX and enzastaurin, significantly reduced PA-mediated lipoapoptosis. More importantly, Huh-7 cells, in which either GSK-3α or GSK-3β isoforms were stably and selectively knocked down by shRNA, displayed resistance to palmitate-induced cytotoxicity. GSK-3 pharmacological inhibitors and shRNA-targeted knockdown of GSK-3α or GSK-3β also suppressed JNK activation by palmitate. JNK activation, in part, promotes lipoapotosis by inducing expression of the pro-apoptotic effector p53-upregulated modulator of apoptosis (PUMA). Consistent with this concept, GSK-3 pharmacologic inhibition also reduced PUMA cellular protein levels during exposure to palmitate. On the other hand, the GSK-3 inhibitors did not prevent PA induction of ER stress.
conclusionsOur results suggest that GSK-3 activation promotes a JNK-dependent cytotoxic signaling cascade culminating in lipoapoptosis.
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Registered trials
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