Journal article
Effect of Expression of Nuclear-Encoded Cytochrome C Oxidase Subunit 4 Isoforms on Metabolic Profiles of Glioma Cells
Metabolites, Vol.12(8), p.748
08/16/2022
DOI: 10.3390/metabo12080748
PMCID: PMC9415780
PMID: 36005623
Abstract
Although often effective at treating newly diagnosed glioblastoma (GBM), increasing evidence suggests that chemo- and radiotherapy-induced alterations in tumor metabolism promote GBM recurrence and aggressiveness, as well as treatment resistance. Recent studies have demonstrated that alterations in glioma cell metabolism, induced by a switch in the isoform expression of cytochrome c oxidase subunit 4 (COX4), a key regulatory subunit of mammalian cytochrome c oxidase, could promote these effects. To understand how the two COX4 isoforms (COX4-1 and COX4-2) differentially affect glioma metabolism, glioma samples harvested from COX4-1- or COX4-2-overexpressing U251 cells were profiled using Gas chromatography–mass spectrometry GC-MS and Liquid Chromatography - Tandem Mass Spectrometry LC-MS/MS metabolomics platforms. The concentration of 362 metabolites differed significantly in the two cell types. The two most significantly upregulated pathways associated with COX4-1 overexpression were purine and glutathione metabolism; the two most significantly downregulated metabolic pathways associated with COX4-1 expression were glycolysis and fatty acid metabolism. Our study provides new insights into how Cytochrome c oxidase (CcO) regulatory subunits affect cellular metabolic networks in GBM and identifies potential targets that may be exploited for therapeutic benefit.
Details
- Title: Subtitle
- Effect of Expression of Nuclear-Encoded Cytochrome C Oxidase Subunit 4 Isoforms on Metabolic Profiles of Glioma Cells
- Creators
- Claudia R. Oliva - University of IowaMd Yousuf Ali - Free Radical & Radiation Biology Program, Department of Radiation Oncology, The University of Iowa, Iowa City, IA 52242, USA Interdisciplinary Graduate Program in Human Toxicology, Department Radiation Oncology, The University of Iowa, Iowa City, IA 52242, USASusanne Flor - University of IowaCorinne E. Griguer - Free Radical & Radiation Biology Program, Department of Radiation Oncology, The University of Iowa, Iowa City, IA 52242, USA Interdisciplinary Graduate Program in Human Toxicology, Department Radiation Oncology, The University of Iowa, Iowa City, IA 52242, USA
- Resource Type
- Journal article
- Publication Details
- Metabolites, Vol.12(8), p.748
- DOI
- 10.3390/metabo12080748
- PMID
- 36005623
- PMCID
- PMC9415780
- NLM abbreviation
- Metabolites
- ISSN
- 2218-1989
- eISSN
- 2218-1989
- Publisher
- MDPI
- Grant note
- RO1 CA127716 / National Institutes of Health Grant
- Language
- English
- Date published
- 08/16/2022
- Academic Unit
- Radiation Oncology
- Record Identifier
- 9984312986402771
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