ArticleCirculation. Heart failure2020
COP9 Signalosome Suppresses RIPK1-RIPK3-Mediated Cardiomyocyte Necroptosis in Mice.
Article in Circulation. Heart failure, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 23 citations in OpenAlex.
- Cullin Deneddylation Suppresses the Necroptotic Pathway in Cardiomyocytes.Frontiers in physiology · 2021Pooled it
- Promoting proteostasis by cAMP/PKA and cGMP/PKG.Trends in molecular medicine · 2025Review
- Mitochondria and myocardial ischemia/reperfusion injury: Effects of Chinese herbal medicine and the underlying mechanisms.Journal of pharmaceutical analysis · 2025Review
- Ubiquitination-mediated protein homeostasis in cardiovascular diseases: molecular mechanisms and therapeutic opportunities.American journal of cardiovascular disease · 2025Review
- Decoding interaction between mitochondria and endoplasmic reticulum in ischemic myocardial injury: targeting natural medicines.Frontiers in pharmacology · 2025Review
- Identification of Necroptosis and Immune Infiltration in Heart Failure Through Bioinformatics Analysis.Journal of inflammation research · 2025Article
- Protein neddylation and its role in health and diseases.Signal transduction and targeted therapy · 2024Review
- The Interplay Between Autophagy and Regulated Necrosis.Antioxidants & redox signaling · 2023Review
- Article
- Necroptosis in heart disease: Molecular mechanisms and therapeutic implications.Journal of molecular and cellular cardiology · 2022Review
- T1AM Attenuates the Hypoxia/Reoxygenation-Induced Necroptosis of H9C2 Cardiomyocytes via RIPK1/RIPK3 Pathway.BioMed research international · 2022Article
- Mitochondrial Quality Control in Cardiac-Conditioning Strategies against Ischemia-Reperfusion Injury.Life (Basel, Switzerland) · 2021Review
- Cell death in head and neck cancer pathogenesis and treatment.Cell death & disease · 2021Review
- NETosis as a Pathogenic Factor for Heart Failure.Oxidative medicine and cellular longevity · 2021Review
- Catecholamine Surges Cause Cardiomyocyte NecroptosisFrontiers in cardiovascular medicine · 2021Article
- The Role of Cullin-RING Ligases in Striated Muscle Development, Function, and Disease.International journal of molecular sciences · 2020Review
- The necessity of NEDD8/Rub1 for vitality and its association with mitochondria-derived oxidative stress.Redox biology · 2020Review
- Neddylation, an Emerging Mechanism Regulating Cardiac Development and Function.Frontiers in physiology · 2020Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundMechanisms governing the induction of heart failure by the impairment of autophagy and the ubiquitin-proteasome system and the molecular pathways to cardiomyocyte necrosis remain incompletely understood. COPS8 is an essential subunit of the COP9 (COnstitutive Photomorphogenesis 9) signalosome, a key regulator of ubiquitination. Mice with cardiomyocyte-restricted knockout of METHODS AND
resultsCompared with littermate control mice, myocardial protein levels of key factors in the necroptotic pathway (RIPK1 [receptor-interacting protein kinase 1], RIPK3, MLKL [mixed lineage kinase-like], the RIPK1-bound RIPK3), protein carbonyls, full-length Casp8 (caspase 8), and BCL2, as well as histochemical staining of superoxide anions were significantly higher but the cleaved Casp8 and the Casp8 activity were significantly lower in Cops8-cko mice. In vivo cardiomyocyte uptake of Evan's blue dye was used as an indicator of necrosis. Cops8-cko mice treated with a RIPK1 kinase inhibitor (Nec-1 [Necrostatin-1]) showed less Evans blue dye uptake (0.005% versus 0.20%;
conclusionsCardiac Cops8/COP9 signalosome malfunction causes RIPK1-RIPK3 dependent, but mitochondrial permeability transition pore independent, cardiomyocyte necroptosis in mice and the COP9 signalosome plays an indispensable role in suppressing cardiomyocyte necroptosis.
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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.