ArticleThe Journal of biological chemistry2015
The Orphan Nuclear Receptor NR4A1 Protects Pancreatic β-Cells from Endoplasmic Reticulum (ER) Stress-mediated Apoptosis.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 38 citations in OpenAlex.
- Positive feedback loop between MAPK and aquaporin 7 regulates autophagy and apoptosis induced by palmitate in RIN-m5f cells.FEBS open bio · 2025Article
- Potential Role of NUR77 in the Aging Retinal Pigment Epithelium and Age-Related Macular Degeneration.Advances in experimental medicine and biology · 2025Review
- PIMT Controls Insulin Synthesis and Secretion through PDX1.International journal of molecular sciences · 2023Article
- Pancreatic islet cell type-specific transcriptomic changes during pregnancy and postpartum.iScience · 2023Article
- The clinical application ofTranslational oncology · 2023Article
- Bioengineered Pancreas-Liver Crosstalk in a Microfluidic Coculture Chip Identifies Human Metabolic Response Signatures in Prediabetic Hyperglycemia.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- The regulation, function, and role of lipophagy, a form of selective autophagy, in metabolic disorders.Cell death & disease · 2022Review
- Adapting Physiology in Functional Human Islet Organogenesis.Frontiers in cell and developmental biology · 2022Article
- Knockout of Nur77 Leads to Amino Acid, Lipid, and Glucose Metabolism Disorders in Zebrafish.Frontiers in endocrinology · 2022Article
- Decreased Abundance of Akkermansia muciniphila Leads to the Impairment of Insulin Secretion and Glucose Homeostasis in Lean Type 2 Diabetes.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021Article
- NR4A1 enhances MKP7 expression to diminish JNK activation induced by ROS or ER-stress in pancreatic β cells for surviving.Cell death discovery · 2021Article
- NR4A1 counteracts JNK activation incurred by ER stress or ROS in pancreatic β-cells for protection.Journal of cellular and molecular medicine · 2020Article
- MKP-5 Relieves Lipotoxicity-Induced Islet β-Cell Dysfunction and Apoptosis via Regulation of Autophagy.International journal of molecular sciences · 2020Article
- Disruption of Beta-Cell Mitochondrial Networks by the Orphan Nuclear Receptor Nor1/Nr4a3.Cells · 2020Article
- Function of Nr4a Orphan Nuclear Receptors in Proliferation, Apoptosis and Fuel Utilization Across Tissues.Cells · 2019Review
- Gene loci associated with insulin secretion in islets from non-diabetic mice.The Journal of clinical investigation · 2019Article
- Nur77 promotes cigarette smoke‑induced autophagic cell death by increasing the dissociation of Bcl2 from Beclin-1.International journal of molecular medicine · 2019Article
- Article
- Linking Endoplasmic Reticular Stress and Alternative Splicing.International journal of molecular sciences · 2018Review
- Inhibition of peptidyl-prolyl cis-trans isomerase B mediates cyclosporin A-induced apoptosis of islet β cells.Experimental and therapeutic medicine · 2018Article
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The role of NR4A1 in apoptosis is controversial. Pancreatic β-cells often face endoplasmic reticulum (ER) stress under adverse conditions such as high free fatty acid (FFA) concentrations and sustained hyperglycemia. Severe ER stress results in β-cell apoptosis. The aim of this study was to analyze the role of NR4A1 in ER stress-mediated β-cell apoptosis and to characterize the related mechanisms. We confirmed that upon treatment with the ER stress inducers thapsigargin (TG) or palmitic acid (PA), the mRNA and protein levels of NR4A1 rapidly increased in both MIN6 cells and mouse islets. NR4A1 overexpression in MIN6 cells conferred resistance to cell loss induced by TG or PA, as assessed by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, and TUNEL assays indicated that NR4A1 overexpression also protected against ER stress-induced apoptosis. This conclusion was further confirmed by experiments exploiting siRNA to knockdown NR4A1 expression in MIN6 cells or exploiting NR4A1 knock-out mice. NR4A1 overexpression in MIN6 cells reduced C/EBP homologous protein (CHOP) expression and Caspase3 activation induced by TG or PA. NR4A1 overexpression in MIN6 cells or mouse islets resulted in Survivin up-regulation. A critical regulatory element was identified in Survivin promoter (-1872 bp to -1866 bp) with a putative NR4A1 binding site; ChIP assays demonstrated that NR4A1 physically associates with the Survivin promoter. In conclusion, NR4A1 protects pancreatic β-cells against ER stress-mediated apoptosis by up-regulating Survivin expression and down-regulating CHOP expression, which we termed as "positive and negative regulation."
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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.