ArticleEBioMedicine2019
Degradation of GRK2 and AKT is an early and detrimental event in myocardial ischemia/reperfusion.
Article in EBioMedicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 34 citations in OpenAlex.
- Beyond β-Adrenergic Receptor Brake: Compartment-Selective GRK2 Programs from Heart Failure to Cardio-Oncology.Kinases and phosphatases · 2026Article
- Stress-Induced calcium mishandling in cardiac (Patho)physiology.Cellular and molecular life sciences : CMLS · 2025Review
- Canonical or non-canonical, all aspects of G protein-coupled receptor kinase 2 in heart failure.Acta physiologica (Oxford, England) · 2025Review
- Global Research Trends and Focus on the Link Between Heart Failure and NLRP3 Inflammasome: A Bibliometric Analysis From 2010 to 2024.Journal of multidisciplinary healthcare · 2025Review
- Efficacy of a cysteine protease inhibitor compared with enalapril in murine heart failure models.iScience · 2024Article
- Cardiomyocyte-specific overexpression of GPR22 ameliorates cardiac injury in mice with acute myocardial infarction.BMC cardiovascular disorders · 2024Article
- Identification of biomarkers related to angiogenesis in myocardial ischemia-reperfusion injury and prediction of potential drugs.PloS one · 2024Article
- Sufentanil inhibits Pin1 to attenuate renal tubular epithelial cell ischemia-reperfusion injury by activating the PI3K/AKT/FOXO1 pathway.International urology and nephrology · 2023Article
- Carboxyl-Functionalized Carbon Nanotubes Loaded with Cisplatin Promote the Inhibition of PI3K/Akt Pathway and Suppress the Migration of Breast Cancer Cells.Pharmaceutics · 2022Article
- Physiological and pathological roles of protein kinase A in the heart.Cardiovascular research · 2022Review
- Observational
- Beneficial Properties of Bromelain.Nutrients · 2021Review
- Targeted inhibition of calpain in mitochondria alleviates oxidative stress-induced myocardial injury.Acta pharmacologica Sinica · 2021Article
- Cardiac GRK2 Protein Levels Show Sexual Dimorphism during Aging and Are Regulated by Ovarian Hormones.Cells · 2021Article
- Review
- Review
- The Suppression of Pin1-Alleviated Oxidative Stress through the p38 MAPK Pathway in Ischemia- and Reperfusion-Induced Acute Kidney Injury.Oxidative medicine and cellular longevity · 2021Article
- G Protein-Coupled Receptor Kinase 2 as Novel Therapeutic Target in Fibrotic Diseases.Frontiers in immunology · 2021Review
- Effect of Quercetin-Loaded Mesoporous Silica Nanoparticles on Myocardial Ischemia-Reperfusion Injury in Rats and Its Mechanism.International journal of nanomedicine · 2021Article
- Modulatory Effect of Myokines on Reactive Oxygen Species in Ischemia/Reperfusion.International journal of molecular sciences · 2020Review
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIdentification of signaling pathways altered at early stages after cardiac ischemia/reperfusion (I/R) is crucial to develop timely therapies aimed at reducing I/R injury. The expression of G protein-coupled receptor kinase 2 (GRK2), a key signaling hub, is up-regulated in the long-term in patients and in experimental models of heart failure. However, whether GRK2 levels change at early time points following myocardial I/R and its functional impact during this period remain to be established.
methodsWe have investigated the temporal changes of GRK2 expression and their potential relationships with the cardioprotective AKT pathway in isolated rat hearts and porcine preclinical models of I/R.
findingsContrary to the maladaptive up-regulation of GRK2 reported at later times after myocardial infarction, successive GRK2 phosphorylation at specific sites during ischemia and early reperfusion elicits GRK2 degradation by the proteasome and calpains, respectively, thus keeping GRK2 levels low during early I/R in rat hearts. Concurrently, I/R promotes decay of the prolyl-isomerase Pin1, a positive regulator of AKT stability, and a marked loss of total AKT protein, resulting in an overall decreased activity of this pro-survival pathway. A similar pattern of concomitant down-modulation of GRK2/AKT/Pin1 protein levels in early I/R was observed in pig hearts. Calpain and proteasome inhibition prevents GRK2/Pin1/AKT degradation, restores bulk AKT pathway activity and attenuates myocardial I/R injury in isolated rat hearts.
interpretationPreventing transient degradation of GRK2 and AKT during early I/R might improve the potential of endogenous cardioprotection mechanisms and of conditioning strategies.
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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 Socratic graph.