ArticleJournal of cellular and molecular medicine2014
ATF4 deficiency protects hepatocytes from oxidative stress via inhibiting CYP2E1 expression.
Article in Journal of cellular and molecular medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 40 citations in OpenAlex.
- Amelioration of Acetaminophen-Induced Hepatic Oxidative Stress and Inflammation by RNAi TargetingCurrent issues in molecular biology · 2025Article
- Taohong Siwu Decoction alleviates high salt-induced calcium overload and ferroptosis in vascular endothelial cells in hypertension by regulating ATF4.Frontiers in nutrition · 2025Article
- ATF4 in cellular stress, ferroptosis, and cancer.Archives of toxicology · 2024Review
- Renoprotective effect ofIranian journal of basic medical sciences · 2024Article
- The Intertwined Roles of Oxidative Stress and Endoplasmic Reticulum Stress in Glaucoma.Antioxidants (Basel, Switzerland) · 2022Review
- Endoplasmic Reticulum Stress Signaling and the Pathogenesis of Hepatocarcinoma.International journal of molecular sciences · 2021Review
- Differentially expressed lncRNAs in liver tissues of TX mice with hepatolenticular degeneration.Scientific reports · 2021Article
- ATF4 leads to glaucoma by promoting protein synthesis and ER client protein load.Nature communications · 2020Article
- Identification of five genes in endoplasmic reticulum (ER) stress-apoptosis pathways in yellow catfish Pelteobagrus fulvidraco and their transcriptional responses to dietary lipid levels.Fish physiology and biochemistry · 2019Article
- Endoplasmic reticulum stress signalling - from basic mechanisms to clinical applications.The FEBS journal · 2019Review
- Fat Mass and Obesity Associated (Nutrients · 2018Review
- ATF4 overexpression induces early onset of hyperlipidaemia and hepatic steatosis and enhances adipogenesis in zebrafish.Scientific reports · 2017Article
- p32 is Required for Appropriate Interleukin-6 Production Upon LPS Stimulation and Protects Mice from Endotoxin Shock.EBioMedicine · 2017Article
- High fat diet-induced changes of mouse hepatic transcription and enhancer activity can be reversed by subsequent weight loss.Scientific reports · 2017Article
- Activating Transcription Factor 4 (ATF4) modulates Rho GTPase levels and function via regulation of RhoGDIα.Scientific reports · 2016Article
- Liver-specific Gene Inactivation of the Transcription Factor ATF4 Alleviates Alcoholic Liver Steatosis in Mice.The Journal of biological chemistry · 2016Article
- Single ingestion of soy β-conglycinin induces increased postprandial circulating FGF21 levels exerting beneficial health effects.Scientific reports · 2016Article
- Tumor suppressor BTG1 promotes PRMT1-mediated ATF4 function in response to cellular stress.Oncotarget · 2016Article
- Mechanistic review of drug-induced steatohepatitis.Toxicology and applied pharmacology · 2015Review
- The effect of alcohol and hydrogen peroxide on liver hepcidin gene expression in mice lacking antioxidant enzymes, glutathione peroxidase-1 or catalase.Biomolecules · 2015Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Activating transcription factor (ATF) 4 is involved in the regulation of oxidative stress in fibroblasts and neurons. The role of ATF4 in hepatocytes, however, is unknown. The aim of this study was to investigate the role of ATF4 in hepatocytes in oxidative stress under a high-fat diet (HFD). Here, we showed that palmitate-stimulated reactive oxygen species (ROS) production and triglyceride (TG) accumulation is blocked by ATF4 deficiency in primary hepatocytes. Consistently, HFD-induced oxidative stress, TG accumulation and expression of cytochrome P450, family 2, subfamily, polypeptide 1 (CYP2E1) are also blocked by knocking down ATF4 expression in the mouse liver. This suggests that ATF4 might regulate oxidative stress via CYP2E1 under an HFD. In addition, we observed that expression of CYP2E1 is indirectly regulated by ATF4 in a cAMP-responsive element binding protein (CREB)-dependent manner, which can directly activate the CYP2E1 promoter activity. Notably, ATF4-stimulated ROS production is inhibited in vivo by treatment with diallyl sulphide, a selective CYP2E1 inhibitor. Finally, we showed that ATF4 expression in the liver is responsible for the protective effects against HFD-induced CYP2E1 expression, oxidative stress, and TG accumulation. Taken together, these observations suggest that ATF4 is a novel regulator of oxidative stress as well as accumulation of TG in response to HFD.
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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.