Summary of Study ST002080
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 PR001320. The data can be accessed directly via it's Project DOI: 10.21228/M8399B This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.
Study ID | ST002080 |
Study Title | Effects of Ferroptosis on the Metabolome in Cardiac Cells: The Role of Glutaminolysis |
Study Type | GCMS |
Study Summary | Ferroptosis is a novel iron-dependent regulated cell death mechanism that affects cell metabolism; however, a detailed metabolomic analysis of ferroptotic cells is not yet available. Here, we elucidated the metabolome of H9c2 cardioblasts by gas chromatography-mass spectrometry during ferroptosis induced by RSL3, a GPX4 inhibitor, in the presence of ferrostatin-1 (a ferroptosis inhibitor), XJB-5-131 (a mitochondrial-targeted ROS scavenger), or TSM-1005-44 (a newly developed cellular ROS scavenger). Results demonstrated that RSL3 decreased the levels of amino acids involved in glutathione synthesis more than two-fold. In contrast, saturated fatty acids levels were markedly increased in RSL3-challenged cells, with no effects on unsaturated fatty acids. RSL3 significantly altered the levels of mitochondrial tricarboxylic acid cycle intermediates; isocitrate and 2-oxoglutarate were found to increase, whereas succinate was significantly decreased in RSL3-challenged cells. Ferrostatin-1, XJB-5-131, and TSM-1005-44 prevented RSL3-induced cell death and conserved the metabolomic profile of the cells. Since 2-oxoglutarate is involved in the regulation of ferroptosis, particularly through glutamine metabolism, we further assessed the role of glutaminolysis in ferroptosis in H9c2 cardioblasts. Genetic silencing of GLS1, which encodes the K-type mitochondrial glutaminase (glutaminase C), protected against ferroptosis in the early stage. In conclusion, our study demonstrates that RSL3-induced ferroptosis impairs the metabolome of H9c2 cardioblasts. |
Institute | University of Puerto Rico, School of Medicine |
Department | Physiology |
Laboratory | Cardiovascular Physiology, DR. Sabzali Javadov's Lab |
Last Name | Rodriguez-Graciani |
First Name | Keishla M |
Address | Medical Sciences Campus, Main Building, 6th Floor, Department of Physiology, San Juan, Puerto Rico, 00936-5067, USA |
keishla.rodriguez20@upr.edu | |
Phone | 7877582525x26888 |
Submit Date | 2022-02-08 |
Num Groups | 8 |
Publications | https://www.mdpi.com/1476010, Antioxidants 2022, 11(2), 278; https://doi.org/10.3390/antiox11020278 |
Raw Data Available | Yes |
Raw Data File Type(s) | cdf |
Analysis Type Detail | GC-MS |
Release Date | 2022-02-22 |
Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Combined analysis:
Analysis ID | AN003394 |
---|---|
Analysis type | MS |
Chromatography type | GC |
Chromatography system | Shimadzu GCMS-QP2010 ultra |
Column | Shimadzu SH-RXI (30m x 0.25mm,0.25um) |
MS Type | EI |
MS instrument type | Single quadrupole |
MS instrument name | Shimadzu QP2010 Ultra |
Ion Mode | POSITIVE |
Units | mM |
MS:
MS ID: | MS003161 |
Analysis ID: | AN003394 |
Instrument Name: | Shimadzu QP2010 Ultra |
Instrument Type: | Single quadrupole |
MS Type: | EI |
MS Comments: | Raw chromatography data were obtained and processed in GC-MS Labsolution Postrun Analysis software (Shimadzu Scientific Instruments, Inc., Columbia, MD) for identification of metabolites from their electron impact mass spectra by comparison to the database (NIST14/2014/EPA/NIH) [26]. Peak integration for all metabolites and multiple searches in the mass spectral library database resulted in a final database of 52 metabolic features chosen for this analysis. To assess analytical accuracy and precision, an external quality evaluation was performed using 2-fluorobiphenyl spiked into derivatization blank samples before running on the GC-MS. The quantitative analysis corresponding to the metabolite concentrations in each sample was calculated based on the internal standard in mM. A table in the format of comma-delimited (* csv) was created and uploaded to MetaboAnalyst.ca. |
Ion Mode: | POSITIVE |