ArticleThe Journal of clinical investigation2015
PHD2/3-dependent hydroxylation tunes cardiac response to β-adrenergic stress via phospholamban.
Article in The Journal of clinical investigation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
20 citing papers in PubMed, 30 citations in OpenAlex.
- Exosomal Preconditioning of Human iPSC-Derived Cardiomyocytes Beneficially Alters Cardiac Electrophysiology and Micro RNA Expression.International journal of molecular sciences · 2024Article
- PHD3 inhibits colon cancer cell metastasis through the occludin-p38 pathway.Acta biochimica et biophysica Sinica · 2023Article
- Review: Precision Medicine Approaches for Genetic Cardiomyopathy: Targeting Phospholamban R14del.Current heart failure reports · 2022Review
- PHD3 inhibits cell proliferation through hydroxylation of PAX2 at proline 9.Acta biochimica et biophysica Sinica · 2022Article
- Article
- Clinical Potential of Hypoxia Inducible Factors Prolyl Hydroxylase Inhibitors in Treating Nonanemic Diseases.Frontiers in pharmacology · 2022Review
- PHDs/CPT1B/VDAC1 axis regulates long-chain fatty acid oxidation in cardiomyocytes.Cell reports · 2021Article
- Role of Hypoxia-Inducible Factors in Regulating Right Ventricular Function and Remodeling during Chronic Hypoxia-induced Pulmonary Hypertension.American journal of respiratory cell and molecular biology · 2020Article
- Lack of activity of recombinant HIF prolyl hydroxylases (PHDs) on reported non-HIF substrates.eLife · 2019Article
- Article
- Prolyl Hydroxylase Domain-2 Protein Regulates Lipopolysaccharide-Induced Vascular Inflammation.The American journal of pathology · 2019Article
- Analysis of Effect ofFrontiers in pharmacology · 2019Article
- PHD3 regulates glucose metabolism by suppressing stress-induced signalling and optimising gluconeogenesis and insulin signalling in hepatocytes.Scientific reports · 2018Article
- α-Ketoglutarate prevents skeletal muscle protein degradation and muscle atrophy through PHD3/ADRB2 pathway.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2018Article
- PHD3 is a transcriptional coactivator of HIF-1α in nucleus pulposus cells independent of the PKM2-JMJD5 axis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2017Article
- New Insights into Protein Hydroxylation and Its Important Role in Human Diseases.Biochimica et biophysica acta · 2016Review
- Targeting EPO and EPO receptor pathways in anemia and dysregulated erythropoiesis.Expert opinion on therapeutic targets · 2016Review
- PHD2: from hypoxia regulation to disease progression.Hypoxia (Auckland, N.Z.) · 2016Review
- Repair Injured Heart by Regulating Cardiac Regenerative Signals.Stem cells international · 2016Review
- Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
Ischemic heart disease is the leading cause of heart failure. Both clinical trials and experimental animal studies demonstrate that chronic hypoxia can induce contractile dysfunction even before substantial ventricular damage, implicating a direct role of oxygen in the regulation of cardiac contractile function. Prolyl hydroxylase domain (PHD) proteins are well recognized as oxygen sensors and mediate a wide variety of cellular events by hydroxylating a growing list of protein substrates. Both PHD2 and PHD3 are highly expressed in the heart, yet their functional roles in modulating contractile function remain incompletely understood. Here, we report that combined deletion of Phd2 and Phd3 dramatically decreased expression of phospholamban (PLN), resulted in sustained activation of calcium/calmodulin-activated kinase II (CaMKII), and sensitized mice to chronic β-adrenergic stress-induced myocardial injury. We have provided evidence that thyroid hormone receptor-α (TR-α), a transcriptional regulator of PLN, interacts with PHD2 and PHD3 and is hydroxylated at 2 proline residues. Inhibition of PHDs increased the interaction between TR-α and nuclear receptor corepressor 2 (NCOR2) and suppressed Pln transcription. Together, these observations provide mechanistic insight into how oxygen directly modulates cardiac contractility and suggest that cardiac function could be modulated therapeutically by tuning PHD enzymatic activity.
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What OpenQuestion holds
Registered trials
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.