ArticleJournal of the American College of Cardiology2010
Doxycycline attenuates protein aggregation in cardiomyocytes and improves survival of a mouse model of cardiac proteinopathy.
Article in Journal of the American College of Cardiology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 32 citations in OpenAlex.
- Review
- Role of the Alpha-B-Crystallin Protein in Cardiomyopathic Disease.International journal of molecular sciences · 2024Review
- Keeping the beat against time: Mitochondrial fitness in the aging heart.Frontiers in aging · 2022Review
- Article
- Ube2v1 Positively Regulates Protein Aggregation by Modulating Ubiquitin Proteasome System Performance Partially Through K63 Ubiquitination.Circulation research · 2020Article
- Neuromuscular Diseases Due to Chaperone Mutations: A Review and Some New Results.International journal of molecular sciences · 2020Review
- PDE1 inhibition facilitates proteasomal degradation of misfolded proteins and protects against cardiac proteinopathy.Science advances · 2019Article
- Article
- Myofibrillar Myopathies: New Perspectives from Animal Models to Potential Therapeutic Approaches.Journal of neuromuscular diseases · 2017Review
- COP9 signalosome controls the degradation of cytosolic misfolded proteins and protects against cardiac proteotoxicity.Circulation research · 2015Article
- Class III PI3K-mediated prolonged activation of autophagy plays a critical role in the transition of cardiac hypertrophy to heart failure.Journal of cellular and molecular medicine · 2015Article
- Improvement of functional recovery of donor heart following cold static storage with doxycycline cardioplegia.Cardiovascular toxicology · 2014Article
- N-acetyl-L-cysteine prevents stress-induced desmin aggregation in cellular models of desminopathy.PloS one · 2013Article
- The ubiquitin-proteasome system and cardiovascular disease.Progress in molecular biology and translational science · 2012Review
- Desmin-related cardiomyopathy: an unfolding story.American journal of physiology. Heart and circulatory physiology · 2011Review
- Enhancement of proteasomal function protects against cardiac proteinopathy and ischemia/reperfusion injury in mice.The Journal of clinical investigation · 2011Article
- The role of the proteasome in heart disease.Biochimica et biophysica acta · 2011Review
- Protein quality control in heart disease: using established drugs to target novel mechanisms.Journal of the American College of Cardiology · 2010Article
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7 authors at 1 institution in 1 country.
Funding
Abstract
objectivesThe goal of this pre-clinical study was to assess the therapeutic efficacy of doxycycline (Doxy) for desmin-related cardiomyopathy (DRC) and to elucidate the potential mechanisms involved.
backgroundDRC, exemplifying cardiac proteinopathy, is characterized by intrasarcoplasmic protein aggregation and cardiac insufficiency. No effective treatment for DRC is available presently. Doxy was shown to attenuate aberrant intranuclear aggregation and toxicity of misfolded proteins in noncardiac cells and animal models of other proteinopathies.
methodsMice and cultured neonatal rat cardiomyocytes with transgenic (TG) expression of a human DRC-linked missense mutation R120G of αB-crystallin (CryAB(R120G)) were used for testing the effect of Doxy. Doxy was administered via drinking water (6 mg/ml) initiated at 8 or 16 weeks of age.
resultsDoxy treatment initiated at 16 weeks of age significantly delayed the premature death of CryAB(R120G) TG mice, with a median lifespan of 30.4 weeks (placebo group, 25 weeks; p < 0.01). In another cohort of CryAB(R120G) TG mice, Doxy treatment initiated at 8 weeks of age significantly attenuated cardiac hypertrophy in 1 month. Further investigation revealed that Doxy significantly reduced the abundance of CryAB-positive microscopic aggregates, detergent-resistant CryAB oligomers, and total ubiquitinated proteins in CryAB(R120G) TG hearts. In cell culture, Doxy treatment dose-dependently suppressed the formation of both microscopic protein aggregates and detergent-resistant soluble CryAB(R120G) oligomers and reversed the up-regulation of p62 protein induced by adenovirus-mediated CryAB(R120G) expression.
conclusionsDoxy suppresses CryAB(R120G)-induced aberrant protein aggregation in cardiomyocytes and prolongs CryAB(R120G)-based DRC mouse survival.
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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.