ArticleThe Journal of biological chemistry2010
Long chain acyl-CoA synthetase-3 is a molecular target for peroxisome proliferator-activated receptor delta in HepG2 hepatoma cells.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 42 citations in OpenAlex.
- ACSL3 inhibits ferroptosis in gastric cancer through the activation of unfolded protein response following endoplasmic reticulum stress.Cell death & disease · 2026Article
- PPARδ: An underappreciated tumor accelerator in pancreatic ductal adenocarcinoma.Cancer letters · 2026Review
- A Novel PPARG R212W Variant Causes Familial Partial Lipodystrophy Type 3: Clinical Presentation and Functional Characterization.International journal of molecular sciences · 2026Article
- The Diagnostic Value of ACSL1, ACSL4, and ACSL5 and the Clinical Potential of an ACSL Inhibitor in Non-Small-Cell Lung Cancer.Cancers · 2024Article
- Ferroptosis inhibition by oleic acid mitigates iron-overload-induced injury.Cell chemical biology · 2024Article
- Article
- Targeting Features of Curaxin CBL0137 on Hematological Malignancies In Vitro and In Vivo.Biomedicines · 2023Article
- Fatty Acids Metabolism: The Bridge Between Ferroptosis and Ionizing Radiation.Frontiers in cell and developmental biology · 2021Review
- Molecular Cloning, Characterization, and Expression Regulation of Acyl-CoA Synthetase 6 Gene and Promoter in Common CarpInternational journal of molecular sciences · 2020Article
- Immunohistochemical staining reveals differential expression of ACSL3 and ACSL4 in hepatocellular carcinoma and hepatic gastrointestinal metastases.Bioscience reports · 2020Article
- Metabolic Remodeling as a Way of Adapting to Tumor Microenvironment (TME), a Job of Several Holders.Advances in experimental medicine and biology · 2020Review
- Whole-Exome Sequencing Reveals New Potential Mutations Genes for Primary Mucosa-Associated Lymphoid Tissue Lymphoma Arising From the Kidney.Frontiers in oncology · 2020Article
- Quercetin Improving Lipid Metabolism by Regulating Lipid Metabolism Pathway of Ileum Mucosa in Broilers.Oxidative medicine and cellular longevity · 2020Article
- Transcriptomic Responses in the Livers and Jejunal Mucosa of Pigs under Different Feeding Frequencies.Animals : an open access journal from MDPI · 2019Article
- Targeting Long Chain Acyl-CoA Synthetases for Cancer Therapy.International journal of molecular sciences · 2019Review
- Fatty acid activation in carcinogenesis and cancer development: Essential roles of long-chain acyl-CoA synthetases.Oncology letters · 2018Review
- Identification of cellular genes and pathways important for tumorigenicity of hepatocellular carcinoma cell lines by proteomic profiling.Oncotarget · 2017Article
- Long-chain acyl-CoA synthetase 6 regulates lipid synthesis and mitochondrial oxidative capacity in human and rat skeletal muscle.The Journal of physiology · 2017Article
- Identification of Hepatic Lysophosphatidylcholine Acyltransferase 3 as a Novel Target Gene Regulated by Peroxisome Proliferator-activated Receptor δ.The Journal of biological chemistry · 2017Article
- Fatty Acid Oxidation Mediated by Acyl-CoA Synthetase Long Chain 3 Is Required for Mutant KRAS Lung Tumorigenesis.Cell reports · 2016Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
ACSL3 is a member of the long chain acyl-CoA synthetase (ACSL) family that plays key roles in fatty acid metabolism in various tissues in an isozyme-specific manner. Our previous studies showed that ACSL3 was transcriptionally up-regulated by the cytokine oncostatin M (OSM) in HepG2 cells, accompanied by reduced cellular triglyceride content and enhanced beta-oxidation. In this study, we investigated the molecular mechanism underlying the OSM-induced activation of ACSL3 gene transcription in HepG2 cells. We showed that OSM treatment resulted in a coordinated elevation of mRNA levels of ACSL3 and peroxisome proliferator-activated receptor delta (PPARdelta). The effect of OSM on ACSL3 mRNA expression was inhibited by cellular depletion of PPARdelta. By utilizing a PPARdelta agonist, L165041, we demonstrated that activation of PPARdelta led to increases in ACSL3 promoter activity, mRNA level, and protein level in HepG2 cells. Analysis of the ACSL3 promoter sequence identified two imperfect PPAR-responsive elements (PPRE) located in the ACSL3 promoter region -944 to -915, relative to the transcription start site. The up-regulation of ACSL3 promoter activity by PPARdelta was abolished by deletion of this PPRE-containing region or mutation to disrupt the binding sites. Direct interactions of PPARdelta with ACSL3-PPRE sequences were demonstrated by gel mobility shift and chromatin immunoprecipitation assays. Finally, we provided in vivo evidence showing that activation of PPARdelta by L165041 in hamsters increased ACSL3 mRNA and protein levels in the liver. These new findings define ACSL3 as a novel molecular target of PPARdelta in HepG2 cells and provide a regulatory mechanism for ACSL3 transcription in liver tissue.
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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.