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.

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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.

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Study IDST002080
Study TitleEffects of Ferroptosis on the Metabolome in Cardiac Cells: The Role of Glutaminolysis
Study TypeGCMS
Study SummaryFerroptosis 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
DepartmentPhysiology
LaboratoryCardiovascular Physiology, DR. Sabzali Javadov's Lab
Last NameRodriguez-Graciani
First NameKeishla M
AddressMedical Sciences Campus, Main Building, 6th Floor, Department of Physiology, San Juan, Puerto Rico, 00936-5067, USA
Emailkeishla.rodriguez20@upr.edu
Phone7877582525x26888
Submit Date2022-02-08
Num Groups8
Publicationshttps://www.mdpi.com/1476010, Antioxidants 2022, 11(2), 278; https://doi.org/10.3390/antiox11020278
Raw Data AvailableYes
Raw Data File Type(s)cdf
Analysis Type DetailGC-MS
Release Date2022-02-22
Release Version1
Keishla M Rodriguez-Graciani Keishla M Rodriguez-Graciani
https://dx.doi.org/10.21228/M8399B
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Factors:

Subject type: Cultured cells; Subject species: Rattus norvegicus (Factor headings shown in green)

mb_sample_id local_sample_id Treatment
SA196497Control_ 2Control
SA196498Control_ 5Control
SA196499Control_ 1Control
SA196500Control_ 4Control
SA196501Control_ 3Control
SA196502Fer1-2Ferrostatin-1
SA196503Fer1-3Ferrostatin-1
SA196504Fer1-6Ferrostatin-1
SA196505Fer1-1Ferrostatin-1
SA196506Fer1-4Ferrostatin-1
SA196507Fer1-5Ferrostatin-1
SA196508RSL3_6RSL3
SA196509RSL3_1RSL3
SA196510RSL3_3RSL3
SA196511RSL3_2RSL3
SA196512RSL3_4RSL3
SA196513RSL3_5RSL3
SA196514RF_1RSL3 + Ferrostatin-1
SA196515RF_2RSL3 + Ferrostatin-1
SA196516RF_3RSL3 + Ferrostatin-1
SA196517RF_6RSL3 + Ferrostatin-1
SA196518RF_4RSL3 + Ferrostatin-1
SA196519RF_5RSL3 + Ferrostatin-1
SA196520RT_2RSL3 + TSM-1005-44
SA196521RT_4RSL3 + TSM-1005-44
SA196522RT_5RSL3 + TSM-1005-44
SA196523RT_3RSL3 + TSM-1005-44
SA196524RT_1RSL3 + TSM-1005-44
SA196525RX_2RSL3 + XJB-5-131
SA196526RX_1RSL3 + XJB-5-131
SA196527RX_3RSL3 + XJB-5-131
SA196528RX_6RSL3 + XJB-5-131
SA196529RX_5RSL3 + XJB-5-131
SA196530RX_4RSL3 + XJB-5-131
SA196531TSM_1TSM-1005-44
SA196532TSM_6TSM-1005-44
SA196533TSM_3TSM-1005-44
SA196534TSM_4TSM-1005-44
SA196535TSM_5TSM-1005-44
SA196536XJB_1XJB-5-131
SA196537XJB_2XJB-5-131
SA196538XJB_5XJB-5-131
SA196539XJB_4XJB-5-131
SA196540XJB_3XJB-5-131
Showing results 1 to 44 of 44
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