Summary of Study ST000576
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR000424. The data can be accessed directly via it's Project DOI: 10.21228/M87S4H This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Study ID | ST000576 |
| Study Title | Effects of the Kinase Inhibitor Sorafenib on Heart Metabolism In Vivo using Non-targeted Metabolomics Analysis tissue). |
| Study Summary | The human kinome consists of ~500 kinases, including 150 proposed as therapeutic targets. progression, cell death, differentiation, and survival. It is not surprising, then, that new tyrosine kinase inhibitors (TKIs) developed to treat cancer also exhibit cardiotoxicity, including sorafenib. We hypothesized that sorafenib cardiotoxicity is related to its deleterious effects on specific cardiac metabolic pathways given the critical role of TKs in cardiac metabolism. FVB/N mice (10/group) were challenged with sorafenib or vehicle control daily for two weeks. Echocardiographic assessment of the heart identified systolic dysfunction consistent with cardiotoxicity compared to vehicle treated controls. Cardiac, skeletal muscle, liver, and serum were flash frozen and prepped for non-targeted GC-MS metabolomics analysis. Compared to vehicle treated controls, sorafenib-treated hearts exhibited significant alterations in 11 metabolites, including markedly altered taurine/hypotaurine metabolism by pathway enrichment analysis (25-fold enrichment). These studies identify sorafenib-induced alterations in cardiac alanine and taurine/hypotaurine metabolic. Interventions to rescue or prevent sorafenib-related cardiotoxicity warrant consideration of therapies targeting the taurine/hypotaurine deficiency identified in the current study. |
| Institute | University of North Carolina at Chapel Hill |
| Department | McAllister heart Institute, Department of Internal medicine |
| Laboratory | Multiple Centers |
| Last Name | Willis |
| First Name | Monte |
| Address | 111 Mason Farm road, Chapel Hill, North Carolina, 27599-7126, USA |
| monte_willis@med.unc.edu | |
| Phone | 919-360-7599 |
| Submit Date | 2017-03-24 |
| Study Comments | Heart, Liver, Skeletal Muscle (Gastrocnemius), Serum |
| Analysis Type Detail | GC-MS |
| Release Date | 2018-04-10 |
| Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Project:
| Project ID: | PR000424 |
| Project DOI: | doi: 10.21228/M87S4H |
| Project Title: | Effects of the Kinase Inhibitor Sorafenib on Heart, Muscle, Liver, and Serum Metabolism In Vivo using Non-targeted Metabolomics Analysis Mice |
| Project Type: | GC-MS non targeted analysis |
| Project Summary: | Non targeted metabolomic analysis on samples from rats expressing human amylin. |
| Institute: | University of North Carolina at Chapel Hill |
| Department: | McAllister heart Institute, Department of Internal medicine |
| Laboratory: | Multiple Centers |
| Last Name: | Willis |
| First Name: | Monte |
| Address: | 111 Mason Farm road, Chapel Hill, North Carolina, 27599-7126, USA |
| Email: | monte_willis@med.unc.edu |
| Phone: | 919-360-7599 |
| Funding Source: | NIH, Fondation Leducq |
Subject:
| Subject ID: | SU000599 |
| Subject Type: | Animal |
| Subject Species: | Mus musculus |
| Taxonomy ID: | 10090 |
| Species Group: | Mammal |
Factors:
Subject type: Animal; Subject species: Mus musculus (Factor headings shown in green)
| mb_sample_id | local_sample_id | Vehicle (PBS) Control Treatment |
|---|---|---|
| SA030404 | 30mg/kg Sor 5 | 30 mg/kg Sorafenib Treatment |
| SA030405 | 30mg/kg Sor 4 | 30 mg/kg Sorafenib Treatment |
| SA030406 | 30mg/kg Sor 3 | 30 mg/kg Sorafenib Treatment |
| SA030407 | 30mg/kg Sor 6 | 30 mg/kg Sorafenib Treatment |
| SA030408 | 30mg/kg Sor 8 | 30 mg/kg Sorafenib Treatment |
| SA030409 | 30mg/kg Sor 10 | 30 mg/kg Sorafenib Treatment |
| SA030410 | 30mg/kg Sor 9 | 30 mg/kg Sorafenib Treatment |
| SA030411 | 30mg/kg Sor 2 | 30 mg/kg Sorafenib Treatment |
| SA030412 | 30mg/kg Sor 7 | 30 mg/kg Sorafenib Treatment |
| SA030413 | 30mg/kg Sor 1 | 30 mg/kg Sorafenib Treatment |
| SA030414 | PBS Ctl 5 | Vehicle (PBS) Control Treatment |
| SA030415 | PBS Ctl 4 | Vehicle (PBS) Control Treatment |
| SA030416 | PBS Ctl 3 | Vehicle (PBS) Control Treatment |
| SA030417 | PBS Ctl 2 | Vehicle (PBS) Control Treatment |
| SA030418 | PBS Ctl 6 | Vehicle (PBS) Control Treatment |
| SA030419 | PBS Ctl 7 | Vehicle (PBS) Control Treatment |
| SA030420 | PBS Ctl 10 | Vehicle (PBS) Control Treatment |
| SA030421 | PBS Ctl 9 | Vehicle (PBS) Control Treatment |
| SA030422 | PBS Ctl 8 | Vehicle (PBS) Control Treatment |
| SA030423 | PBS Ctl 1 | Vehicle (PBS) Control Treatment |
| Showing results 1 to 20 of 20 |
Collection:
| Collection ID: | CO000593 |
| Collection Summary: | Cardiac tissue was harvested and flash frozen in a liquid nitrogen cooled biopress |
| Sample Type: | Muscle |
Treatment:
| Treatment ID: | TR000613 |
| Treatment Summary: | Fraction of cardiac tissue weighed (25äóñ50 mg wet weight), then the finely cut up tissue quickly added to fresh pre-made buffer (50 % acetyl-nitrile, 50 % water, 0.3% formic acid) at a standard concentration of 25 mg/475 microlieters (mcl) buffer then fully homogenized on ice for 20 seconds and placed on dry ice/stored at - 80C |
Sample Preparation:
| Sampleprep ID: | SP000606 |
| Sampleprep Summary: | The samples were crash deprotonized by methanol precipitation and spiked with D27-deuterated myristic acid (D27-C14:0) as an internal standard for retention-time locking and dried. The trimethylsilyl-D27-C14:0 standard retention time (RT) was set at 16.727 min. Reactive carbonyls were stabilized at 50C with methoxyamine hydrochloride in dry pyridine. Metabolites were made volatile with TMS groups using N-methyl-N-(trimethylsilyl) trifluoroacetamide or MSTFA with catalytic trimethylchlorosilane at 50C. |
Combined analysis:
| Analysis ID | AN000886 |
|---|---|
| Analysis type | MS |
| Chromatography type | GC |
| Chromatography system | Agilent 6890N |
| Column | Agilent DB5-MS (15m x 0.25mm,0.25um) |
| MS Type | EI |
| MS instrument type | Single quadrupole |
| MS instrument name | Agilent 5975 |
| Ion Mode | POSITIVE |
| Units | Peak values (Log transformed) |
Chromatography:
| Chromatography ID: | CH000629 |
| Chromatography Summary: | GC/MS methods follow previous studies using a 6890 N GC connected to a 5975 Inert single quadrupole MS (Agilent Technologies, Santa Clara, CA) (Bonikos et al. 1975; Fiehn 2008; Kind et al. 2009). The two wall-coated, open-tubular GC columns connected in series are both from J&W/Agilent (part 122äóñ5512), DB5-MS, 15 meters in length, 0.25 mm in diameter, with an 0.25-l m luminal film. Positive ions generated with conventional electron-ionization at 70 eV are scanned broadly from 600 to 50 m/z in the detector throughout the 45 min cycle time. |
| Instrument Name: | Agilent 6890N |
| Column Name: | Agilent DB5-MS (15m x 0.25mm,0.25um) |
| Chromatography Type: | GC |
MS:
| MS ID: | MS000788 |
| Analysis ID: | AN000886 |
| Instrument Name: | Agilent 5975 |
| Instrument Type: | Single quadrupole |
| MS Type: | EI |
| Ion Mode: | POSITIVE |
