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dc.contributor.authorSantos jiménez, Juan de los
dc.contributor.authorRosales, Tracy
dc.contributor.authorKo, Bookyung
dc.contributor.authorMárquez-Gómez, Javier 
dc.contributor.authorBerardinis, Ralph J. de
dc.contributor.authorMates-Sánchez, José Manuel 
dc.date.accessioned2022-09-09T06:35:22Z
dc.date.available2022-09-09T06:35:22Z
dc.date.created2022-07-17
dc.date.issued2012-07-19
dc.identifier.citationAbcam Conference cancer and Metabolism 2022es_ES
dc.identifier.urihttps://hdl.handle.net/10630/24923
dc.description.abstractMany tumors use Gln for both energy generation and as a biosynthetic precursor. Glutaminases (GAs) catalyze the first step of glutaminolysis by converting glutamine (Gln) into glutamate and ammonia in the mitochondria. In humans, two genes encode for glutaminases: GLS and GLS2. We examined the metabolic consequences of inhibiting GLS activity in glioma cells by using the clinically relevant inhibitor CB-839. We treated three glioblastoma (GBM) cell lines with CB-839 and performed untargeted metabolomics and isotope tracing experiments using U-13C-labeled Gln and 15N-labeled Gln in the amido group to ascertain the metabolic fates of Gln carbon and nitrogen. Untargeted metabolomics results showed that CB-839 treatment significantly depleted tricarboxylic acid cycle (TCAC) intermediates and related metabolites in the three human glioblastoma cell lines assayed. This result was also confirmed by a lower labeling from U-13C- Gln in these metabolites. U-13C- Gln tracing also revealed reductive carboxylation-related labeling in these cell lines, and this pathways was also suppressed by CB-839. Metabolomics results showed an accumulation of the de novo purine biosynthesis intermediates inosine monophosphate and/or AICAR, and a decrease in uridine monophosphate, while 15N-Gln tracing results showed a decreased labeling from Gln amido group in AMP, GMP, UMP and CTP in T98G cell line when treated with CB-839. Finally, metabolomics showed higher levels of trimethyllysine and, in T98G cells, a 22-fold increase in 5-methyl-cytosine.es_ES
dc.description.sponsorshipUniversidad de Málaga. Campus de Excelencia Internacional Andalucía Tech.es_ES
dc.language.isoenges_ES
dc.rightsinfo:eu-repo/semantics/openAccesses_ES
dc.subjectGliomases_ES
dc.subjectCánceres_ES
dc.subject.otherCanceres_ES
dc.subject.otherMetabolismes_ES
dc.subject.otherMetabolomicses_ES
dc.subject.otherGlioblastomaes_ES
dc.subject.otherGlutaminasees_ES
dc.titleMetabolic changes upon GLS inhibition by CB-839 in glioma cell lineses_ES
dc.typeinfo:eu-repo/semantics/conferenceObjectes_ES
dc.centroFacultad de Cienciases_ES
dc.relation.eventtitleAbcam Conference Cancer and Metabolism 2022es_ES
dc.relation.eventplaceLondon, UKes_ES
dc.relation.eventdate17-19 Julio 2022es_ES


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