ArticleThe Journal of clinical investigation2011
Enhancement of proteasomal function protects against cardiac proteinopathy and ischemia/reperfusion injury in mice.
Article in The Journal of clinical investigation, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 127 papers, 1 of them a synthesis that pooled it.
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Who cites it
127 citing papers in PubMed, 1 synthesis or guideline pooled it, 188 citations in OpenAlex.
- The Heart of the Alzheimer's: A Mindful View of Heart Disease.Frontiers in physiology · 2020Pooled it
- Integrated protein quality-control pathways regulate free α-globin in murine β-thalassemia.Blood · 2012Trial
- Mitophagy Facilitates Cytosolic Proteostasis to Preserve Cardiac Function.Circulation research · 2026Article
- Stimulating proteasomal degradation in human proteinopathies.The FEBS journal · 2026Review
- PKA-Mediated Proteasome Activation Protects Against Cardiac Remodeling and Heart Failure During Systolic Overload.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Review
- The R120G knock-in mutation in αB-crystallin is insufficient to induce cardiomyopathy in mice.American journal of physiology. Heart and circulatory physiology · 2026Article
- Ubiquitin-Related Proteostatic Programs in Cycling Fibroblast-Lineage Remodeling After Myocardial Ischemic Injury: A Hypothesis Informed by Single-Cell and Spatial Transcriptomics.International journal of molecular sciences · 2026Review
- Transcriptome remodeling of mouse hearts during postnatal cardiac maturation and under proteotoxic stress.Molecular biology reports · 2026Article
- Not Just PA28γ: What We Know About the Role of PA28αβ in Carcinogenesis.Biomolecules · 2025Review
- Proteostasis and Its Role in Disease Development.Cell biochemistry and biophysics · 2025Review
- Gain and loss of the centrosomal protein taxilin-beta influences cardiac proteostasis and stress.Journal of molecular and cellular cardiology · 2025Article
- Promoting proteostasis by cAMP/PKA and cGMP/PKG.Trends in molecular medicine · 2025Review
- From bench to bedside: elucidating VEGF(R) inhibitor-related heart failure in cancer treatment.Journal of translational medicine · 2025Article
- Psmb8 inhibits mitochondrial fission and alleviates myocardial ischaemia/reperfusion injury by targeting Drp1 degradation.Cell death & disease · 2024Article
- Review
- Genetic blockade of the activation of 26S proteasomes by PKA is well tolerated by mice at baseline.American journal of cardiovascular disease · 2024Article
- Genetic insights into the effect of trace elements on cardiovascular diseases: multi-omics Mendelian randomization combined with linkage disequilibrium score regression analysis.Frontiers in immunology · 2024Article
- S14-Phosphorylated RPN6 Mediates Proteasome Activation by PKA and Alleviates Proteinopathy.Circulation research · 2023Article
- Overexpression of Nfe2l1 increases proteasome activity and delays vision loss in a preclinical model of human blindness.Science advances · 2023Article
67 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
The ubiquitin-proteasome system degrades most intracellular proteins, including misfolded proteins. Proteasome functional insufficiency (PFI) has been observed in proteinopathies, such as desmin-related cardiomyopathy, and implicated in many common diseases, including dilated cardiomyopathy and ischemic heart disease. However, the pathogenic role of PFI has not been established. Here we created inducible Tg mice with cardiomyocyte-restricted overexpression of proteasome 28 subunit α (CR-PA28αOE) to investigate whether upregulation of the 11S proteasome enhances the proteolytic function of the proteasome in mice and, if so, whether the enhancement can rescue a bona fide proteinopathy and protect against ischemia/reperfusion (I/R) injury. We found that CR-PA28αOE did not alter the homeostasis of normal proteins and cardiac function, but did facilitate the degradation of a surrogate misfolded protein in the heart. By breeding mice with CR-PA28αOE with mice representing a well-established model of desmin-related cardiomyopathy, we demonstrated that CR-PA28αOE markedly reduced aberrant protein aggregation. Cardiac hypertrophy was decreased, and the lifespan of the animals was increased. Furthermore, PA28α knockdown promoted, whereas PA28α overexpression attenuated, accumulation of the mutant protein associated with desmin-related cardiomyopathy in cultured cardiomyocytes. Moreover, CR-PA28αOE limited infarct size and prevented postreperfusion cardiac dysfunction in mice with myocardial I/R injury. We therefore conclude that benign enhancement of cardiac proteasome proteolytic function can be achieved by CR-PA28αOE and that PFI plays a major pathogenic role in cardiac proteinopathy and myocardial I/R injury.
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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.