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| Status |
Public on Jun 01, 2021 |
| Title |
Identifying metabolic adaptations of rat cardiomyocytes in response to cardiotoxicity |
| Organism |
Rattus norvegicus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Improvements in the diagnosis and treatment of cancer has revealed the long-term side effects of chemotherapeutics, particularly cardiotoxicity. Current clinical measures to track cardiotoxicity are insufficient to diagnose damage before it has been done, necessitating new, early biomarkers of cardiotoxicity. Here, we collected paired transcriptomics and metabolomics data characterizing in vitro cardiotoxicity to three compounds: 5-fluorouracil, acetaminophen, and doxorubicin. Standard gene enrichment and metabolomics approaches identify some commonly affected pathways and metabolites but are not able to readily identify mechanisms of cardiotoxicity. Here, we integrate this paired data with a genome-scale metabolic network reconstruction (GENRE) of the heart to identify shifted metabolic functions, unique metabolic reactions, and changes in flux in metabolic reactions in response to these compounds. Using this approach, we are able to confirm known mechanisms of doxorubicin-induced cardiotoxicity and provide hypotheses for mechanisms of cardiotoxicity for 5-fluorouracil and acetaminophen.
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| Overall design |
RNA was extracted from primary rat neonatal cardiomyocytes that were treated for 6 or 24 hours with 10mM 5-fluorouracil, 2.5 mM acetaminophen, or 1.25 uM doxorubicin with 6-7 replicates per condition and timepoint. Two controls were used: DMSO1 for the 5-fluorouracil condition and DMSO2 for the acetaminophen and doxorubicin condition.
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| Contributor(s) |
Dougherty BV, Rawls KD, Jenior ML, Chun B, Nagdas S, Saucerman JJ, Kolling GL, Wallqvist A, Papin JA |
| Citation missing |
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| Submission date |
Feb 17, 2021 |
| Last update date |
Jun 01, 2021 |
| Contact name |
Jason Papin |
| E-mail(s) |
[email protected]
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| Organization name |
University of Virginia
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| Department |
Biomedical Engineering
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| Lab |
Papin Lab
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| Street address |
415 Lane Rd
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| City |
Charlottesville |
| State/province |
VA |
| ZIP/Postal code |
22908 |
| Country |
USA |
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| Platforms (1) |
| GPL18694 |
Illumina HiSeq 2500 (Rattus norvegicus) |
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| Samples (65)
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| Relations |
| BioProject |
PRJNA702469 |
| SRA |
SRP306869 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE166957_differential_expression.xlsx |
7.1 Mb |
(ftp)(http) |
XLSX |
| GSE166957_raw_gene_counts.csv.gz |
1.5 Mb |
(ftp)(http) |
CSV |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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