ArticleJournal of hepatology2012
Cdc42 and Rac1 are major contributors to the saturated fatty acid-stimulated JNK pathway in hepatocytes.
Article in Journal of hepatology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 86 citations in OpenAlex.
- Proteomics and Metabolomics Reveal Novel Impacts of Choline Supply on Calf Hepatocytes Experiencing Accumulation During a Fatty Acid Challenge.Metabolites · 2026Article
- β-Sitosterol ameliorates metabolic dysfunction-associated steatohepatitis by targeting the RAC1/mTOR/TFEB axis thus activating lipophagy-lysosomal pathway.Acta pharmacologica Sinica · 2026Article
- Fatty Acid-binding Protein 4 Exacerbates Blood-brain Barrier Disruption Through the JNK/c-Jun/MMP12 Pathway After Traumatic Brain Injury.Molecular neurobiology · 2025Article
- Targeting ASK1 by CS17919 alleviates kidney- and liver-related diseases in murine models.Animal models and experimental medicine · 2025Article
- Two sides of the same coin: Non-alcoholic fatty liver disease and atherosclerosis.Vascular pharmacology · 2024Review
- The Role of Cdc42 in the Insulin and Leptin Pathways Contributing to the Development of Age-Related Obesity.Nutrients · 2023Review
- Lysosomal-associated protein transmembrane 5 ameliorates non-alcoholic steatohepatitis by promoting the degradation of CDC42 in mice.Nature communications · 2023Article
- Liver saturated fat content associates with hepatic DNA methylation in obese individuals.Clinical epigenetics · 2023Article
- Characteristic gene expression in the liver monocyte-macrophage-DC system is associated with the progression of fibrosis in NASH.Frontiers in immunology · 2023Article
- Stress kinases in the development of liver steatosis and hepatocellular carcinoma.Molecular metabolism · 2021Review
- Protein Phosphatase 4 Promotes Hepatocyte Lipoapoptosis by Regulating RAC1/MLK3/JNK Pathway.Oxidative medicine and cellular longevity · 2021Article
- Nonalcoholic Steatohepatitis Promoting Kinases.Seminars in liver disease · 2020Review
- Pediatric obesity-related asthma: A prototype of pediatric severe non-T2 asthma.Pediatric pulmonology · 2020Article
- Macronutrients and the Adipose-Liver Axis in Obesity and Fatty Liver.Cellular and molecular gastroenterology and hepatology · 2019Review
- The Regulation of JNK Signaling Pathways in Cell Death through the Interplay with Mitochondrial SAB and Upstream Post-Translational Effects.International journal of molecular sciences · 2018Review
- To die or not to die: death signaling in nonalcoholic fatty liver disease.Journal of gastroenterology · 2018Review
- Identification of key genes in non‑alcoholic fatty liver disease progression based on bioinformatics analysis.Molecular medicine reports · 2018Article
- New insights into the role and mechanism of c-Jun-N-terminal kinase signaling in the pathobiology of liver diseases.Hepatology (Baltimore, Md.) · 2018Review
- Integrated Analysis and Identification of Novel Biomarkers in Parkinson's Disease.Frontiers in aging neuroscience · 2018Article
- A Protein Scaffold Coordinates SRC-Mediated JNK Activation in Response to Metabolic Stress.Cell reports · 2017Article
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
BACKGROUND &
aimsSaturated free fatty acid (SFA)-stimulated c-Jun NH(2)-terminal kinase (JNK) activation is associated with the pathogenesis of non-alcoholic fatty liver disease (NAFLD). However, the mechanisms responsible for the effects of SFA are incompletely understood. The goal of this study was to determine the molecular mechanisms by which SFA induce JNK activation in hepatocytes.
methodsWe used siRNA-mediated knockdown in Hepa1c1c7 and AML12 cell lines, as well as primary mouse hepatocytes for these studies.
resultsThe current model for JNK activation by SFA involves endoplasmic reticulum (ER) stress, which induces JNK activation through an inositol requiring enzyme 1 (IRE1α) Apoptosis Regulating Kinase 1 (ASK1)-dependent mechanism. Here, we find that SFA-induced JNK activation is not inhibited in the absence of IRE1α and ASK1. Instead we show that activation of the small GTP-binding proteins Cdc42 and Rac1 is required for SFA-stimulated MLK3-dependent activation of JNK in hepatocytes. In addition, we demonstrate that SFA-induced cell death in hepatocytes is independent of IRE1α, but dependent on Cdc42, Rac1, and MLK3.
conclusionsOur results demonstrate that Cdc42 and Rac1, rather than ER stress, are important components of a SFA-stimulated signaling pathway that regulates MLK3-dependent activation of JNK in hepatocytes.
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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.