ArticleNature medicine2016
CaMKII is a RIP3 substrate mediating ischemia- and oxidative stress-induced myocardial necroptosis.
Article in Nature medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 455 papers, 1 of them a synthesis that pooled it.
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Who cites it
455 citing papers in PubMed, 1 synthesis or guideline pooled it, 777 citations in OpenAlex.
- Evidence that tirzepatide protects against diabetes-related cardiac damages.Cardiovascular diabetology · 2024 · on this mapPooled it
- The Deubiquitinase UCHL1 Drives Susceptibility to Atrial Fibrillation by Stabilizing CaMKII-δ.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- LncRNA DLX6-AS1 promotes necroptosis through PI3K/AKT/mTOR signaling pathway in myocardial ischemia/reperfusion injury mice.Scientific reports · 2026Article
- Exploring the role of CaMKII in exercise-induced cardioprotection.Human cell · 2026Review
- Multiple organ dysfunction syndrome: molecular mechanisms and therapeutic strategies.Signal transduction and targeted therapy · 2026Review
- Review
- Mitochondrial Dysfunction at the Crossroads of Necroptosis: Mechanisms, Molecular Mediators, and Therapeutic Opportunities.Journal of cellular and molecular medicine · 2026Review
- Role of β-adrenergic signaling in the development of Porphyromonas gingivalis lipopolysaccharide-induced cardiac dysfunction in mice.Scientific reports · 2026Article
- Short-term blockade of E-prostanoid 3 receptor mitigates necroinflammation and ameliorates ischemia/reperfusion- and doxorubicin-induced acute myocardial injury.Basic research in cardiology · 2026Article
- FERPIR promotes cardiomyocyte survival and attenuates cardiac remodeling after myocardial infarction.Cell death & disease · 2026Article
- Non-canonical PPARα Agonism by Arjunolic Acid Mitigates Cardiomyocyte PANoptosis Through a Novel PPARα/CRYAB/IKKα Axis During Pathological Cardiac Hypertrophy.Cardiovascular toxicology · 2026Article
- SWATH-MS for discovery of early biomarkers of drug-induced cardiotoxicity using an animal doxorubicin model.Cardio-oncology (London, England) · 2026Article
- TRIM28 Is an E3 Ligase of IRP2 Suppressing Ischemia/Reperfusion-Induced Myocardial Ferroptosis.Circulation · 2026Article
- Nanocarrier-Based Therapeutic Strategies in Myocardial Ischemia-Reperfusion Injury: A Systematic Review of Preclinical Evidence.Biomedicines · 2026Review
- MLKL Deficiency Stabilizes RIP3 and Aggravates Myocardial Injury by Promoting Apoptosis and Pyroptosis.Current issues in molecular biology · 2026Article
- Adenovirus phagocytosis by neutrophils triggers a pro-inflammatory response.PLoS pathogens · 2026Article
- Distinct types of regulated cell death in atherosclerosis.Journal of pharmaceutical analysis · 2026Review
- The critical role of necroptosis in oil cyst formation associated with autologous fat transplantation.Cell communication and signaling : CCS · 2026Article
- BACH2 ameliorates cell apoptosis and autophagy as a molecular switch of BCL-2/Beclin-1 complex in myocardial infarction.Apoptosis : an international journal on programmed cell death · 2026Article
- Ferroptosis in cardiovascular diseases: molecular mechanisms and a novel therapeutic target.Molecular biomedicine · 2026Review
395 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
17 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Regulated necrosis (necroptosis) and apoptosis are crucially involved in severe cardiac pathological conditions, including myocardial infarction, ischemia-reperfusion injury and heart failure. Whereas apoptotic signaling is well defined, the mechanisms that underlie cardiomyocyte necroptosis remain elusive. Here we show that receptor-interacting protein 3 (RIP3) triggers myocardial necroptosis, in addition to apoptosis and inflammation, through activation of Ca(2+)-calmodulin-dependent protein kinase (CaMKII) rather than through the well-established RIP3 partners RIP1 and MLKL. In mice, RIP3 deficiency or CaMKII inhibition ameliorates myocardial necroptosis and heart failure induced by ischemia-reperfusion or by doxorubicin treatment. RIP3-induced activation of CaMKII, via phosphorylation or oxidation or both, triggers opening of the mitochondrial permeability transition pore and myocardial necroptosis. These findings identify CaMKII as a new RIP3 substrate and delineate a RIP3-CaMKII-mPTP myocardial necroptosis pathway, a promising target for the treatment of ischemia- and oxidative stress-induced myocardial damage and heart failure.
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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.