ArticlePharmaceutical research2014
Interindividual variability in the cardiac expression of anthracycline reductases in donors with and without Down syndrome.
Article in Pharmaceutical research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 20 citations in OpenAlex.
- Drugs Metabolism-Related Genes Variants Impact on Anthracycline-Based Chemotherapy Induced Subclinical Cardiotoxicity in Breast Cancer Patients.International journal of molecular sciences · 2025Article
- Carbonyl reductase 1: a novel regulator of blood pressure in Down syndrome.Bioscience reports · 2025Article
- Carbonyl reductase 1 amplifies glucocorticoid action in adipose tissue and impairs glucose tolerance in lean mice.Molecular metabolism · 2021Article
- Comparative analysis of the DYRK1A-SRSF6-TNNT2 pathway in myocardial tissue from individuals with and without Down syndrome.Experimental and molecular pathology · 2019Article
- Insights into the transcriptional regulation of the anthracycline reductase AKR7A2 in human cardiomyocytes.Toxicology letters · 2019Article
- CBR1 rs9024 genotype status impacts the bioactivation of loxoprofen in human liver.Biopharmaceutics & drug disposition · 2018Article
- Systematic proteome and proteostasis profiling in human Trisomy 21 fibroblast cells.Nature communications · 2017Article
- Carbonyl reductase 1 catalyzes 20β-reduction of glucocorticoids, modulating receptor activation and metabolic complications of obesity.Scientific reports · 2017Article
- Successful recovery and allogeneic stem cell transplant following chemotherapy-induced severe cardiomyopathy: literature review of management and prognostic factors.BMJ case reports · 2016Review
- Article
- Development of a CART Model to Predict the Synthesis of Cardiotoxic Daunorubicinol in Heart Tissue Samples From Donors With and Without Down Syndrome.Journal of pharmaceutical sciences · 2016Article
- Pharmacokinetics of Chemotherapeutic Drugs in Pediatric Patients With Down Syndrome and Leukemia.Journal of pediatric hematology/oncology · 2016Review
- Role of DNA Methylation on the Expression of the Anthracycline Metabolizing Enzyme AKR7A2 in Human Heart.Cardiovascular toxicology · 2016Article
- Cardiotoxicity of anthracycline therapy: current perspectives.Archives of medical science : AMS · 2016Article
- Activation of the Constitutive Androstane Receptor Increases the Therapeutic Index of CHOP in Lymphoma Treatment.Molecular cancer therapeutics · 2016Article
- Characterization of the Canine Anthracycline-Metabolizing Enzyme Carbonyl Reductase 1 (cbr1) and the Functional Isoform cbr1 V218.Drug metabolism and disposition: the biological fate of chemicals · 2015Article
- Chromosome 21-derived hsa-miR-155-5p regulates mitochondrial biogenesis by targeting Mitochondrial Transcription Factor A (TFAM).Biochimica et biophysica acta · 2015Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
purposeThe intracardiac synthesis of anthracycline alcohol metabolites (e.g., daunorubicinol) contributes to the pathogenesis of anthracycline-related cardiotoxicity. Cancer patients with Down syndrome (DS) are at increased risk for anthracycline-related cardiotoxicity. We profiled the expression of anthracycline metabolizing enzymes in hearts from donors with- and without- DS.
methodsCardiac expression of CBR1, CBR3, AKR1A1, AKR1C3 and AKR7A2 was examined by quantitative real time PCR, quantitative immunoblotting, and enzyme activity assays using daunorubicin. The CBR1 polymorphism rs9024 was investigated by allelic discrimination with fluorescent probes. The contribution of CBRs/AKRs proteins to daunorubicin reductase activity was examined by multiple linear regression.
resultsCBR1 was the most abundant transcript (average relative expression; DS: 81%, non-DS: 58%), and AKR7A2 was the most abundant protein (average relative expression; DS: 38%, non-DS: 35%). Positive associations between cardiac CBR1 protein levels and daunorubicin reductase activity were found for samples from donors with- and without- DS. Regression analysis suggests that sex, CBR1, AKR1A1, and AKR7A2 protein levels were significant contributors to cardiac daunorubicin reductase activity. CBR1 rs9024 genotype status impacts on cardiac CBR1 expression in non-DS hearts.
conclusionsCBR1, AKR1A1, and AKR7A2 protein levels point to be important determinants for predicting the synthesis of cardiotoxic daunorubicinol in heart.
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