ArticleBMC systems biology2013
Signaling dynamics of palmitate-induced ER stress responses mediated by ATF4 in HepG2 cells.
Article in BMC systems biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 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
27 citing papers in PubMed, 45 citations in OpenAlex.
- Trial
- Fibroblast growth factor 21 is a hepatokine involved in MASLD progression.United European gastroenterology journal · 2024Article
- DWN12088, A Prolyl-tRNA Synthetase Inhibitor, Alleviates Hepatic Injury in Nonalcoholic Steatohepatitis.Diabetes & metabolism journal · 2024Article
- Artichoke (Cynara scolymus L.) water extract alleviates palmitate-induced insulin resistance in HepG2 hepatocytes via the activation of IRS1/PI3K/AKT/FoxO1 and GSK-3β signaling pathway.BMC complementary medicine and therapies · 2023Article
- Ectopic Lipid Accumulation Correlates with Cellular Stress in Rabbit Blastocysts from Diabetic Mothers.International journal of molecular sciences · 2023Article
- Harnessing conserved signaling and metabolic pathways to enhance the maturation of functional engineered tissues.NPJ Regenerative medicine · 2022Review
- Metabolomic Analysis of Human Astrocytes in Lipotoxic Condition: Potential Biomarker Identification by Machine Learning Modeling.Biomolecules · 2022Article
- Role of Activating Transcription Factor 4 in Murine Choroidal Neovascularization Model.International journal of molecular sciences · 2021Article
- Amino Acid Composition of Amniotic Fluid during the Perinatal Period Reflects Mother's Fat and Carbohydrate Intake.Nutrients · 2021Article
- Activation of NRF2 and ATF4 Signaling by the Pro-Glutathione Molecule I-152, a Co-Drug ofAntioxidants (Basel, Switzerland) · 2021Article
- Protein Phosphatase 4 Promotes Hepatocyte Lipoapoptosis by Regulating RAC1/MLK3/JNK Pathway.Oxidative medicine and cellular longevity · 2021Article
- Article
- Dipeptidyl peptidase-4 inhibitor protects against non-alcoholic steatohepatitis in mice by targeting TRAIL receptor-mediated lipoapoptosis via modulating hepatic dipeptidyl peptidase-4 expression.Scientific reports · 2020Article
- Transient receptor potential ion channel TRPM2 promotes AML proliferation and survival through modulation of mitochondrial function, ROS, and autophagy.Cell death & disease · 2020Article
- ATF6 Is a Critical Determinant of CHOP Dynamics during the Unfolded Protein Response.iScience · 2020Article
- Palmitic Acid-Rich High-Fat Diet Exacerbates Experimental Pulmonary Fibrosis by Modulating Endoplasmic Reticulum Stress.American journal of respiratory cell and molecular biology · 2019Article
- Identification of a time-varying intracellular signalling model through data clustering and parameter selection: application to NF-[inline-formula removed]B signalling pathway induced by LPS in the presence of BFA.IET systems biology · 2019Article
- Concomitant Nrf2- and ATF4-activation by Carnosic Acid Cooperatively Induces Expression of Cytoprotective Genes.International journal of molecular sciences · 2019Article
- IL-24 Promotes Apoptosis through cAMP-Dependent PKA Pathways in Human Breast Cancer Cells.International journal of molecular sciences · 2018Article
- Response to Persistent ER Stress in Plants: A Multiphasic Process That Transitions Cells from Prosurvival Activities to Cell Death.The Plant cell · 2018Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundPalmitic acid, the most common saturated free fatty acid, has been implicated in ER (endoplasmic reticulum) stress-mediated apoptosis. This lipoapotosis is dependent, in part, on the upregulation of the activating transcription factor-4 (ATF4). To better understand the mechanisms by which palmitate upregulates the expression level of ATF4, we integrated literature information on palmitate-induced ER stress signaling into a discrete dynamic model. The model provides an in silico framework that enables simulations and predictions. The model predictions were confirmed through further experiments in human hepatocellular carcinoma (HepG2) cells and the results were used to update the model and our current understanding of the signaling induced by palmitate.
resultsThe three key things from the in silico simulation and experimental results are: 1) palmitate induces different signaling pathways (PKR (double-stranded RNA-activated protein kinase), PERK (PKR-like ER kinase), PKA (cyclic AMP (cAMP)-dependent protein kinase A) in a time dependent-manner, 2) both ATF4 and CREB1 (cAMP-responsive element-binding protein 1) interact with the Atf4 promoter to contribute to a prolonged accumulation of ATF4, and 3) CREB1 is involved in ER-stress induced apoptosis upon palmitate treatment, by regulating ATF4 expression and possibly Ca2+ dependent-CaM (calmodulin) signaling pathway.
conclusionThe in silico model helped to delineate the essential signaling pathways in palmitate-mediated apoptosis.
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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.