ArticleBritish journal of pharmacology2012
Regulation of apoptosis in HL-1 cardiomyocytes by phosphorylation of the receptor tyrosine kinase EphA2 and protection by lithocholic acid.
Article in British journal of pharmacology, 2012. 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
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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, 25 citations in OpenAlex.
- Bile acid signaling in health and disease.Molecular biomedicine · 2026Review
- Emerging insights of bile acids in cardiovascular physiology and disease: from molecular mechanisms to therapeutic potential.Frontiers in pharmacology · 2026Review
- The bidirectional regulatory mechanism of gut microbiota metabolites on myocardial injury in heart failure from the perspective of the gut-heart axis: a review.Frontiers in microbiology · 2025Review
- Recent advances of the Ephrin and Eph family in cardiovascular development and pathologies.iScience · 2024Review
- From dried bear bile to molecular investigation of differential effects of bile acids inBrain, behavior, & immunity - health · 2023Review
- The Relationship Between Atrial Fibrillation and Intestinal Flora With Its Metabolites.Frontiers in cardiovascular medicine · 2022Review
- EphrinA1-Fc Attenuates Ventricular Remodeling and Dysfunction in Chronically Nonreperfused WT but not EphA2-R-M mice.International journal of molecular sciences · 2020Article
- Atheroprotective effects of 17β-oestradiol are mediated by peroxisome proliferator-activated receptor γ in human coronary artery smooth muscle cells.Archives of medical sciences. Atherosclerotic diseases · 2020Article
- Regulatory T-cells regulate neonatal heart regeneration by potentiating cardiomyocyte proliferation in a paracrine manner.Theranostics · 2019Article
- TGR5 activation induces cytoprotective changes in the heart and improves myocardial adaptability to physiologic, inotropic, and pressure-induced stress in mice.Cardiovascular therapeutics · 2018Article
- Translational systems pharmacology-based predictive assessment of drug-induced cardiomyopathy.CPT: pharmacometrics & systems pharmacology · 2018Article
- Cardiac thromboxane A2 receptor activation does not directly induce cardiomyocyte hypertrophy but does cause cell death that is prevented with gentamicin and 2-APB.BMC pharmacology & toxicology · 2014Article
- UniPR129 is a competitive small molecule Eph-ephrin antagonist blocking in vitro angiogenesis at low micromolar concentrations.British journal of pharmacology · 2014Article
- EphA2-receptor deficiency exacerbates myocardial infarction and reduces survival in hyperglycemic mice.Cardiovascular diabetology · 2014Article
- Binding and function of phosphotyrosines of the Ephrin A2 (EphA2) receptor using synthetic sterile α motif (SAM) domains.The Journal of biological chemistry · 2014Article
- HERG K+ channel-dependent apoptosis and cell cycle arrest in human glioblastoma cells.PloS one · 2014Article
- Deletion of the EphA2 receptor exacerbates myocardial injury and the progression of ischemic cardiomyopathy.Frontiers in physiology · 2014Article
- Ephrin-Eph signaling as a potential therapeutic target for the treatment of myocardial infarction.Medical hypotheses · 2013Article
- Amino acid conjugates of lithocholic acid as antagonists of the EphA2 receptor.Journal of medicinal chemistry · 2013Article
- Crosstalk between apoptosis and autophagy: molecular mechanisms and therapeutic strategies in cancer.Journal of cell death · 2013Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeHeart failure and atrial fibrillation are associated with apoptosis of cardiomyocytes, suggesting common abnormalities in pro-apoptotic cardiac molecules. Activation of the receptor tyrosine kinase EphA2 causes apoptosis in vitro, and dysregulation of EphA2-dependent signalling is implicated in LEOPARD and Noonan syndromes associated with cardiomyopathy. Molecular pathways and regulation of EphA2 signalling in the heart are poorly understood. Here we elucidated the pathways of EphA2-dependent apoptosis and evaluated a therapeutic strategy to prevent EphA2 activation and cardiac cell death. EXPERIMENTAL APPROACH: EphA2 signalling was studied in an established model of doxazosin-induced apoptosis in HL-1 cells. Apoptosis was measured with TUNEL assays and as cell viability using a formazan method. Western blotting and siRNA for EphA2 were also used. KEY
resultsApoptosis induced by doxazosin (EC(50) = 17.3 μM) was associated with EphA2 activation through enhanced phosphorylation (2.2-fold). Activation of pro-apoptotic downstream factors, phospho-SHP-2 (3.9-fold), phospho-p38 MAPK (2.3-fold) and GADD153 (1.6-fold) resulted in cleavage of caspase 3. Furthermore, two anti-apoptotic enzymes were suppressed (focal adhesion kinase, by 41%; phospho-Akt, by 78%). Inactivation of EphA2 with appropriate siRNA mimicked pro-apoptotic effects of doxazosin. Finally, administration of lithocholic acid (LCA) protected against apoptosis by increasing EphA2 protein levels and decreasing EphA2 phosphorylation. CONCLUSIONS AND IMPLICATIONS: EphA2 phosphorylation and activation of SHP-2 are critical steps in apoptosis. Reduction of EphA2 phosphorylation by LCA may represent a novel approach for future anti-apoptotic treatment of heart failure and atrial fibrillation.
Indexed as
Identifiers
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.