ArticleJournal of molecular medicine (Berlin, Germany)2015
Loss of Egr-1 sensitizes pancreatic β-cells to palmitate-induced ER stress and apoptosis.
Article in Journal of molecular medicine (Berlin, Germany), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 27 citations in OpenAlex.
- Relationship between plasma atherogenic index and thyroid function: evidence from NHANES 2007-2012.Scientific reports · 2025Article
- Single-cell transcriptomic analysis of canine insulinoma reveals distinct sub-populations of insulin-expressing cancer cells.Veterinary oncology (London, England) · 2025Article
- Glycerol Kinase Drives Hepatic de novo Lipogenesis and Triglyceride Synthesis in Nonalcoholic Fatty Liver by Activating SREBP-1c Transcription, Upregulating DGAT1/2 Expression, and Promoting Glycerol Metabolism.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Shift work promotes adipogenesis via cortisol-dependent downregulation of EGR3-HDAC6 pathway.Cell death discovery · 2024Article
- Identification of endoplasmic reticulum stress-related biomarkers of diabetes nephropathy based on bioinformatics and machine learning.Frontiers in endocrinology · 2023Article
- Transcriptional mechanisms of pancreatic β-cell maturation and functional adaptation.Trends in endocrinology and metabolism: TEM · 2021Review
- Article
- EGR-1 plays a protective role in AMPK inhibitor compound C-induced apoptosis through ROS-induced ERK activation in skin cancer cells.Oncology letters · 2021Article
- Glucose stimulates microRNA-199 expression in murine pancreatic β-cells.The Journal of biological chemistry · 2020Article
- Loss of EGR-1 uncouples compensatory responses of pancreatic β cells.Theranostics · 2020Article
- Egr-1 regulates irradiation-induced autophagy through Atg4B to promote radioresistance in hepatocellular carcinoma cells.Oncogenesis · 2017Article
- Radiation Induced Apoptosis of Murine Bone Marrow Cells Is Independent of Early Growth Response 1 (EGR1).PloS one · 2017Article
- Egr-1 deficiency protects from renal inflammation and fibrosis.Journal of molecular medicine (Berlin, Germany) · 2016Article
- Overexpression of miR-223 Tips the Balance of Pro- and Anti-hypertrophic Signaling Cascades toward Physiologic Cardiac Hypertrophy.The Journal of biological chemistry · 2016Article
- The progress of early growth response factor 1 and leukemia.Intractable & rare diseases research · 2016Review
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
unlabelledPancreatic β-cells are particularly susceptible to fatty-acid-induced endoplasmic reticulum (ER) stress and apoptosis. To understand how β-cells sense fatty acid stimuli and translate into a long-term adaptive response, we investigated whether palmitic acid (PA) regulates early growth response-1 (Egr-1), an immediate-early transcription factor, which is induced by many environmental stimuli and implicated in cell proliferation, differentiation, and apoptosis. We found that Egr-1 was rapidly and transiently induced by PA in MIN6 insulinoma cells, which was accompanied by calcium influx and ERK1/2 phosphorylation. Calcium chelation and MEK1/2 inhibition blocked PA-induced Egr-1 upregulation, suggesting that PA induces Egr-1 expression through a calcium influx-MEK1/2-ERK1/2 cascade. Knockdown of Egr-1 increased PA-induced caspase-3 activation and ER stress markers and decreased PA-induced Akt phosphorylation and insulin secretion and signaling. Akt replenishment and insulin supplementation rescued PA-induced apoptosis in Egr-1 knockdown cells. These results suggest that the absence of Egr-1 loses its ability to couple the short-term insulin/Akt pathway to long-term survival adaptation. Finally, Egr-1-deficient mouse islets are more susceptible to ex vivo stimuli of apoptosis. In human pancreatic tissues, EGR1 expression correlated with expression of ER stress markers and anti-apoptotic gene. In conclusion, Egr-1 is induced by PA and further attempts to rescue β-cells from ER stress and apoptosis through improving insulin/Akt signaling. Our study underscores Egr-1 as a critical early sensor in pancreatic β-cells to translate fatty acid stimuli into a cellular adaptation mechanism. KEY MESSAGE: PA stimulates Egr-1 expression via a calcium influx-MEK1/2-ERK1/2-Elk-1 cascade. Egr-1 attenuates PA-induced ER stress and apoptosis. Egr-1 maintains Akt survival pathway to protect β-cells from PA-induced apoptosis. Egr-1-deficient islets are prone to ex vivo stimuli of apoptosis. Human EGR1 expression correlates with genes for ER stress and anti-apoptosis.
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