ArticleProceedings of the National Academy of Sciences of the United States of America2011
Ischemia-induced calpain activation causes eukaryotic (translation) initiation factor 4G1 (eIF4GI) degradation, protein synthesis inhibition, and neuronal death.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 29 citations in OpenAlex.
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- Single-cell RNA sequencing in stroke and traumatic brain injury: Current achievements, challenges and future perspectives on transcriptomic profiling.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2026Review
- Eukaryotic translation initiation factor 4F: functional properties and physiological role.Nucleic acids research · 2025Review
- Eukaryotic translation initiation factorExperimental and therapeutic medicine · 2024Article
- PA2G4/EBP1 ubiquitination by PRKN/PARKIN promotes mitophagy protecting neuron death in cerebral ischemia.Autophagy · 2024Article
- Extracellular CIRP Induces Calpain Activation in Neurons via PLC-IPMolecular neurobiology · 2023Article
- Astroglia Abnormalities in Post-stroke Mood Disorders.Advances in neurobiology · 2021Review
- Translational Factor eIF4G1 Regulates Glucose Homeostasis and Pancreatic β-Cell Function.Diabetes · 2021Article
- Methyltransferase 3 Mediated miRNA m6A Methylation Promotes Stress Granule Formation in the Early Stage of Acute Ischemic Stroke.Frontiers in molecular neuroscience · 2020Article
- Calcium-Activated Calpain Specifically Cleaves Glutamate Receptor IIA But Not IIB at theThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2019Article
- Enhancing Endogenous Nitric Oxide by Whole Body Periodic Acceleration Elicits Neuroprotective Effects in Dystrophic Neurons.Molecular neurobiology · 2018Article
- Global ischemia induces lysosomal-mediated degradation of mTOR and activation of autophagy in hippocampal neurons destined to die.Cell death and differentiation · 2017Article
- Proteasome inhibitors bortezomib and carfilzomib used for the treatment of multiple myeloma do not inhibit the serine protease HtrA2/Omi.Toxicology research · 2016Article
- Calpain Cleaves Most Components in the Multiple Aminoacyl-tRNA Synthetase Complex and Affects Their Functions.The Journal of biological chemistry · 2015Article
- Cold stress protein RBM3 responds to temperature change in an ultra-sensitive manner in young neurons.Neuroscience · 2015Article
- Role of translation initiation factor 4G in lifespan regulation and age-related health.Ageing research reviews · 2014Review
- The translational repressor eIF4E-binding protein 2 (4E-BP2) correlates with selective delayed neuronal death after ischemia.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2013Article
- Article
- Non-conventional apoptotic response to ionising radiation mediated by N-methyl D-aspartate receptors in immature neuronal cells.International journal of molecular medicine · 2013Article
Corrections and comments
- Erratum issued
- Erratum issued
Authors and funding
11 authors at 5 institutions in 4 countries.
Funding
Abstract
Persistent protein synthesis inhibition (PSI) is a robust predictor of eventual neuronal death following cerebral ischemia. We thus tested the hypothesis that persistent PSI inhibition and neuronal death are causally linked. Neuronal viability strongly correlated with both protein synthesis and levels of eukaryotic (translation) initiation factor 4G1 (eIF4G1). We determined that in vitro ischemia activated calpain, which degraded eIF4G1. Overexpression of the calpain inhibitor calpastatin or eIF4G1 resulted in increased protein synthesis and increased neuronal viability compared with controls. The neuroprotective effect of eIF4G1 overexpression was due to restoration of cap-dependent protein synthesis, as well as protein synthesis-independent mechanisms, as inhibition of protein synthesis with cycloheximide did not completely prevent the protective effect of eIF4G1 overexpression. In contrast, shRNA-mediated silencing of eIF4G1 exacerbated ischemia-induced neuronal injury, suggesting eIF4G1 is necessary for maintenance of neuronal viability. Finally, calpain inhibition following global ischemia in vivo blocked decreases in eIF4G1, facilitated protein synthesis, and increased neuronal viability in ischemia-vulnerable hippocampal CA1 neurons. Collectively, these data demonstrate that calpain-mediated degradation of a translation initiation factor, eIF4G1, is a cause of both persistent PSI and neuronal death.
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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.