ArticleCirculation research2009
p66Shc links alpha1-adrenergic receptors to a reactive oxygen species-dependent AKT-FOXO3A phosphorylation pathway in cardiomyocytes.
Article in Circulation research, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 81 citations in OpenAlex.
- Mitochondria and NLRP3 inflammasome in cardiac hypertrophy.Molecular and cellular biochemistry · 2024Review
- Exploring the Gut-Mitochondrial Axis: p66Shc Adapter Protein and Its Implications for Metabolic Disorders.International journal of molecular sciences · 2024Review
- Molecular mechanisms of endothelial dysfunction in coronary microcirculation dysfunction.Journal of thrombosis and thrombolysis · 2023Review
- Role of oxidative stress and inflammation-related signaling pathways in doxorubicin-induced cardiomyopathy.Cell communication and signaling : CCS · 2023Review
- The role of mitochondria-associated membranes mediated ROS on NLRP3 inflammasome in cardiovascular diseases.Frontiers in cardiovascular medicine · 2022Review
- Aging-Induced Impairment of Vascular Function: Mitochondrial Redox Contributions and Physiological/Clinical Implications.Antioxidants & redox signaling · 2021Review
- Lack of Contribution of p66shc to Pressure Overload-Induced Right Heart Hypertrophy.International journal of molecular sciences · 2020Article
- Akt3 induces oxidative stress and DNA damage by activating the NADPH oxidase via phosphorylation of p47Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- P66Shc and vascular endothelial function.Bioscience reports · 2019Review
- The Antioxidant from Ethanolic Extract ofInternational journal of molecular sciences · 2019Article
- Cathelicidin-related antimicrobial peptide protects against myocardial ischemia/reperfusion injury.BMC medicine · 2019Article
- Mitochondrial regulation of diabetic vascular disease: an emerging opportunity.Translational research : the journal of laboratory and clinical medicine · 2018Review
- Dietary supplementation with ketoacids protects against CKD-induced oxidative damage and mitochondrial dysfunction in skeletal muscle of 5/6 nephrectomised rats.Skeletal muscle · 2018Article
- Role of Beta-adrenergic Receptors and Sirtuin Signaling in the Heart During Aging, Heart Failure, and Adaptation to Stress.Cellular and molecular neurobiology · 2018Review
- Does growth differentiation factor 11 protect against myocardial ischaemia/reperfusion injury? A hypothesis.The Journal of international medical research · 2017Article
- Cardiac GPCR-Mediated EGFR Transactivation: Impact and Therapeutic Implications.Journal of cardiovascular pharmacology · 2017Review
- New aspects of p66Shc in ischaemia reperfusion injury and other cardiovascular diseases.British journal of pharmacology · 2017Review
- Sirtuin1-regulated lysine acetylation of p66Shc governs diabetes-induced vascular oxidative stress and endothelial dysfunction.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Effects of Resveratrol on p66Shc phosphorylation in cultured prostate cells.Translational medicine @ UniSa · 2015Article
- Norepinephrine-induced apoptotic and hypertrophic responses in H9c2 cardiac myoblasts are characterized by different repertoire of reactive oxygen species generation.Redox biology · 2015Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
p66Shc is an adapter protein that is induced by hypertrophic stimuli and has been implicated as a major regulator of reactive oxygen species (ROS) production and cardiovascular oxidative stress responses. This study implicates p66Shc in an alpha(1)-adrenergtic receptor (alpha(1)-AR) pathway that requires the cooperative effects of protein kinase (PK)Cepsilon and PKCdelta and leads to AKT-FOXO3a phosphorylation in cardiomyocytes. alpha(1)-ARs promote p66Shc-YY(239/240) phosphorylation via a ROS-dependent mechanism that is localized to caveolae and requires epidermal growth factor receptor (EGFR) and PKCepsilon activity. alpha(1)-ARs also increase p66Shc-S(36) phosphorylation via an EGFR transactivation pathway involving PKCdelta. p66Shc links alpha(1)-ARs to an AKT signaling pathway that selectively phosphorylates/inactivates FOXO transcription factors and downregulates the ROS-scavenging protein manganese superoxide dismutase (MnSOD); the alpha(1)-AR-p66Shc-dependent pathway involving AKT does not regulate GSK3. Additional studies show that RNA interference-mediated downregulation of endogenous p66Shc leads to the derepression of FOXO3a-regulated genes such as MnSOD, p27Kip1, and BIM-1. p66Shc downregulation also increases proliferating cell nuclear antigen expression and induces cardiomyocyte hypertrophy, suggesting that p66Shc exerts an antihypertrophic action in neonatal cardiomyocytes. The novel alpha(1)-AR- and ROS-dependent pathway involving p66Shc identified in this study is likely to contribute to cardiomyocyte remodeling and the evolution of heart failure.
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Registered trials
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