ArticleAging cell2016
CYP2J2 and its metabolites (epoxyeicosatrienoic acids) attenuate cardiac hypertrophy by activating AMPKα2 and enhancing nuclear translocation of Akt1.
Article in Aging cell, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 40 citations in OpenAlex.
- Construction of a competitive endogenous RNA network and identification of potential regulatory axes in hypertrophic cardiomyopathy.Frontiers in cardiovascular medicine · 2025Article
- Article
- 11-Hydroxyeicosatetraenoics induces cellular hypertrophy in an enantioselective manner.Frontiers in pharmacology · 2024Article
- Increased Soluble Epoxide Hydrolase Activity Positively Correlates with Mortality in Heart Failure Patients with Preserved Ejection Fraction: Evidence from Metabolomics.Phenomics (Cham, Switzerland) · 2023Article
- CYP450 Epoxygenase Metabolites, Epoxyeicosatrienoic Acids, as Novel Anti-Inflammatory Mediators.Molecules (Basel, Switzerland) · 2022Review
- Signaling cascades in the failing heart and emerging therapeutic strategies.Signal transduction and targeted therapy · 2022Review
- Epoxyeicosatrienoic Acids and Fibrosis: Recent Insights for the Novel Therapeutic Strategies.International journal of molecular sciences · 2021Review
- Soluble epoxide hydrolase deficiency attenuates lipotoxic cardiomyopathy via upregulation of AMPK-mTORC mediated autophagy.Journal of molecular and cellular cardiology · 2021Article
- Metabolism pathways of arachidonic acids: mechanisms and potential therapeutic targets.Signal transduction and targeted therapy · 2021Review
- The Role of Epoxyeicosatrienoic Acids in Cardiac Remodeling.Frontiers in physiology · 2021Review
- CYP2J2 Is a Diagnostic and Prognostic Biomarker Associated with Immune Infiltration in Kidney Renal Clear Cell Carcinoma.BioMed research international · 2021Article
- Itaconate prevents abdominal aortic aneurysm formation through inhibiting inflammation via activation of Nrf2.EBioMedicine · 2020Article
- Review
- A Large Scale Systemic RNAi Screen in the Red Flour BeetleG3 (Bethesda, Md.) · 2019Article
- Inhibition of soluble epoxide hydrolase attenuates a high-fat diet-mediated renal injury by activating PAX2 and AMPK.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Regulation of CYP2J2 and EET Levels in Cardiac Disease and Diabetes.International journal of molecular sciences · 2018Review
- AMPKα2 Protects Against the Development of Heart Failure by Enhancing Mitophagy via PINK1 Phosphorylation.Circulation research · 2018Article
- Heme Binding Biguanides Target Cytochrome P450-Dependent Cancer Cell Mitochondria.Cell chemical biology · 2017Article
- CYP2J2 metabolites, epoxyeicosatrienoic acids, attenuate Ang II-induced cardiac fibrotic response by targeting GαJournal of lipid research · 2017Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cytochrome P450 epoyxgenase 2J2 and epoxyeicosatrienoic acids (EETs) are known to protect against cardiac hypertrophy and heart failure, which involve the activation of 5'-AMP-activated protein kinase (AMPK) and Akt. Although the functional roles of AMPK and Akt are well established, the significance of cross talk between them in the development of cardiac hypertrophy and antihypertrophy of CYP2J2 and EETs remains unclear. We investigated whether CYP2J2 and its metabolites EETs protected against cardiac hypertrophy by activating AMPKα2 and Akt1. Moreover, we tested whether EETs enhanced cross talk between AMPKα2 and phosphorylated Akt1 (p-Akt1), and stimulated nuclear translocation of p-Akt1, to exert their antihypertrophic effects. AMPKα2(-/-) mice that overexpressed CYP2J2 in heart were treated with Ang II for 2 weeks. Interestingly, overexpression of CYP2J2 suppressed cardiac hypertrophy and increased levels of atrial natriuretic peptide (ANP) in the heart tissue and plasma of wild-type mice but not AMPKα2(-/-) mice. The CYP2J2 metabolites, 11,12-EET, activated AMPKα2 to induce nuclear translocation of p-Akt1 selectively, which increased the production of ANP and therefore inhibited the development of cardiac hypertrophy. Furthermore, by co-immunoprecipitation analysis, we found that AMPKα2β2γ1 and p-Akt1 interact through the direct binding of the AMPKγ1 subunit to the Akt1 protein kinase domain. This interaction was enhanced by 11,12-EET. Our studies reveal a novel mechanism in which CYP2J2 and EETs enhanced Akt1 nuclear translocation through interaction with AMPKα2β2γ1 and protect against cardiac hypertrophy and suggest that overexpression of CYP2J2 might have clinical potential to suppress cardiac hypertrophy and heart failure.
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