ArticleCirculation research2010
Targeted deletion of the extracellular signal-regulated protein kinase 5 attenuates hypertrophic response and promotes pressure overload-induced apoptosis in the heart.
Article in Circulation research, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 81 citations in OpenAlex.
- Berberine Attenuates Hypertrophic Phenotype in RAF1-Mutant Induced Pluripotent Stem Cell-Derived Cardiomyocytes through Suppression of ERK5-Cyclin D1 Signaling.Cardiovascular drugs and therapy · 2026Article
- Bone and Extracellular Signal-Related Kinase 5 (ERK5).Biomolecules · 2024Review
- Review
- Quercetin alleviates diastolic dysfunction and suppresses adverse pro-hypertrophic signaling in diabetic rats.Frontiers in endocrinology · 2022Article
- Protections of transcription factor BACH2 and natural product myricetin against pathological cardiac hypertrophy and dysfunction.Frontiers in physiology · 2022Article
- Mechanisms of Cardiorenal Protection With SGLT2 Inhibitors in Patients With T2DM Based on Network Pharmacology.Frontiers in cardiovascular medicine · 2022Article
- The MEK5/ERK5 Pathway in Health and Disease.International journal of molecular sciences · 2021Review
- Isoflurane post-conditioning contributes to anti-apoptotic effect after cerebral ischaemia in rats through the ERK5/MEF2D signaling pathway.Journal of cellular and molecular medicine · 2021Article
- A Role for Caveolin-3 in the Pathogenesis of Muscular Dystrophies.International journal of molecular sciences · 2020Review
- Therapeutic potential of targeting kinase inhibition in patients with idiopathic pulmonary fibrosis.Yeungnam University journal of medicine · 2020Article
- Involvement of MEK5/ERK5 signaling pathway in manganese-induced cell injury in dopaminergic MN9D cells.Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS) · 2020Article
- TargetingeLife · 2020Article
- Article
- The role of post-translational modifications in cardiac hypertrophy.Journal of cellular and molecular medicine · 2019Review
- ERK: A Key Player in the Pathophysiology of Cardiac Hypertrophy.International journal of molecular sciences · 2019Review
- Microtubule associated protein 4 phosphorylation leads to pathological cardiac remodeling in mice.EBioMedicine · 2018Article
- A Disintegrin and Metalloprotease-22 Attenuates Hypertrophic Remodeling in Mice Through Inhibition of the Protein Kinase B Signaling Pathway.Journal of the American Heart Association · 2018Article
- Metabolic stress-induced cardiomyopathy is caused by mitochondrial dysfunction due to attenuated Erk5 signaling.Nature communications · 2017Article
- Sub-cellular localization specific SUMOylation in the heart.Biochimica et biophysica acta. Molecular basis of disease · 2017Review
- The role of Epac in the heart.Cellular and molecular life sciences : CMLS · 2017Review
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
rationaleMitogen-activated protein kinase (MAPK) pathways provide a critical connection between extrinsic and intrinsic signals to cardiac hypertrophy. Extracellular signal-regulated protein kinase (ERK)5, an atypical MAPK is activated in the heart by pressure overload. However, the role of ERK5 plays in regulating hypertrophic growth and hypertrophy-induced apoptosis is not completely understood.
objectiveHerein, we investigate the in vivo role and signaling mechanism whereby ERK5 regulates cardiac hypertrophy and hypertrophy-induced apoptosis. METHODS AND
resultsWe generated and examined the phenotypes of mice with cardiomyocyte-specific deletion of the erk5 gene (ERK5(cko)). In response to hypertrophic stress, ERK5(cko) mice developed less hypertrophic growth and fibrosis than controls. However, increased apoptosis together with upregulated expression levels of p53 and Bad were observed in the mutant hearts. Consistently, we found that silencing ERK5 expression or specific inhibition of its kinase activity using BIX02189 in neonatal rat cardiomyocytes (NRCMs) reduced myocyte enhancer factor (MEF)2 transcriptional activity and blunted hypertrophic responses. Furthermore, the inhibition of MEF2 activity in NRCMs using a non-DNA binding mutant form of MEF2 was found to attenuate the ERK5-regulated hypertrophic response.
conclusionsThese results reveal an important function of ERK5 in cardiac hypertrophic remodeling and cardiomyocyte survival. The role of ERK5 in hypertrophic remodeling is likely to be mediated via the regulation of MEF2 activity.
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Registered trials
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