ArticleThe Journal of biological chemistry2016
Hyperglycemic Conditions Prime Cells for RIP1-dependent Necroptosis.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 77 citations in OpenAlex.
- Mitochondrial Dysfunction at the Crossroads of Necroptosis: Mechanisms, Molecular Mediators, and Therapeutic Opportunities.Journal of cellular and molecular medicine · 2026Review
- Cold atmospheric plasma is a promising strategy for treating diabetic retinopathy.Journal of translational medicine · 2025Review
- Role of Necroptosis and Neuroinflammation in CSVD-Associated Cognitive Decline in db/db Mice.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Current understanding of eryptosis: mechanisms, physiological functions, role in disease, pharmacological applications, and nomenclature recommendations.Cell death & disease · 2025Review
- Cell death signaling in human erythron: erythrocytes lose the complexity of cell death machinery upon maturation.Apoptosis : an international journal on programmed cell death · 2025Review
- Redox Regulation and Glucose Metabolism in the Stallion Spermatozoa.Antioxidants (Basel, Switzerland) · 2025Review
- Erythronecroptosis: an overview of necroptosis or programmed necrosis in red blood cells.Molecular and cellular biochemistry · 2024Review
- Regulated Cell Death Pathways in Pathological Cardiac Hypertrophy.Reviews in cardiovascular medicine · 2024Review
- The Role of Necroptosis in Cerebral Ischemic Stroke.Molecular neurobiology · 2024Review
- Non-Apoptotic Programmed Cell Death as Targets for Diabetic Retinal Neurodegeneration.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Metformin attenuates lung ischemia-reperfusion injury and necroptosis through AMPK pathway in type 2 diabetic recipient rats.BMC pulmonary medicine · 2024Article
- Apoptosis and eryptosis: similarities and differences.Apoptosis : an international journal on programmed cell death · 2024Review
- Diabetes Mellitus to Accelerated Atherosclerosis: Shared Cellular and Molecular Mechanisms in Glucose and Lipid Metabolism.Journal of cardiovascular translational research · 2024Review
- NADPH Dynamics: Linking Insulin Resistance and β-Cells Ferroptosis in Diabetes Mellitus.International journal of molecular sciences · 2023Review
- Diabetes Exacerbates Pseudomonas aeruginosa Keratitis in Streptozotocin-Induced and db/db Mice via Altering Programmed Cell Death Pathways.Investigative ophthalmology & visual science · 2023Article
- Mitochondrial Trafficking of MLKL, Bak/Bax, and Drp1 Is Mediated by RIP1 and ROS which Leads to Decreased Mitochondrial Membrane Integrity during the Hyperglycemic Shift to Necroptosis.International journal of molecular sciences · 2023Article
- Role of necroptosis in kidney health and disease.Nature reviews. Nephrology · 2023Review
- Glucose Starvation Inhibits Ferroptosis by Activating the LKB1/AMPK Signaling Pathway and Promotes the High Speed Linear Motility of Dairy Goat Sperm.Animals : an open access journal from MDPI · 2023Article
- Glycolysis: an emerging regulator of osteoarthritis.Frontiers in immunology · 2023Review
- Cardioprotective effect of extracellular vesicles derived from ticagrelor-pretreated cardiomyocyte on hyperglycemic cardiomyocytes through alleviation of oxidative and endoplasmic reticulum stress.Scientific reports · 2022Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Necroptosis is a RIP1-dependent programmed cell death (PCD) pathway that is distinct from apoptosis. Downstream effector pathways of necroptosis include formation of advanced glycation end products (AGEs) and reactive oxygen species (ROS), both of which depend on glycolysis. This suggests that increased cellular glucose may prime necroptosis. Here we show that exposure to hyperglycemic levels of glucose enhances necroptosis in primary red blood cells (RBCs), Jurkat T cells, and U937 monocytes. Pharmacologic or siRNA inhibition of RIP1 prevented the enhanced death, confirming it as RIP1-dependent necroptosis. Hyperglycemic enhancement of necroptosis depends upon glycolysis with AGEs and ROS playing a role. Total levels of RIP1, RIP3, and mixed lineage kinase domain-like (MLKL) proteins were increased following treatment with high levels of glucose in Jurkat and U937 cells and was not due to transcriptional regulation. The observed increase in RIP1, RIP3, and MLKL protein levels suggests a potential positive feedback mechanism in nucleated cell types. Enhanced PCD due to hyperglycemia was specific to necroptosis as extrinsic apoptosis was inhibited by exposure to high levels of glucose. Hyperglycemia resulted in increased infarct size in a mouse model of brain hypoxia-ischemia injury. The increased infarct size was prevented by treatment with nec-1s, strongly suggesting that increased necroptosis accounts for exacerbation of this injury in conditions of hyperglycemia. This work reveals that hyperglycemia represents a condition in which cells are extraordinarily susceptible to necroptosis, that local glucose levels alter the balance of PCD pathways, and that clinically relevant outcomes may depend on glucose-mediated effects on PCD.
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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.