Reductive carboxylation and 2-hydroxyglutarate formation by wild-type IDH2 in breast carcinoma cells

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11110%2F15%3A10296857" target="_blank" >RIV/00216208:11110/15:10296857 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/67985823:_____/15:00446813

Výsledek na webu

<a href="http://dx.doi.org/10.1016/j.biocel.2015.05.012" target="_blank" >http://dx.doi.org/10.1016/j.biocel.2015.05.012</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.biocel.2015.05.012" target="_blank" >10.1016/j.biocel.2015.05.012</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Reductive carboxylation and 2-hydroxyglutarate formation by wild-type IDH2 in breast carcinoma cells

Popis výsledku v původním jazyce

Mitochondrial NADPH-dependent isocitrate dehydrogenase, IDH2, and cytosolic IDH1, catalyze reductive carboxylation of 2-oxoglutarate. Both idh2 and idh1 monoallelic mutations are harbored in grade 2/3 gliomas, secondary glioblastomas and acute myeloid leukemia. Mutant IDH1/IDH2 enzymes were reported to form an oncometabolite R-2-hydroxyglutarate (2HG), further strengthening malignancy. We quantified CO2-dependent reductive carboxylation glutaminolysis (RCG) and CO2-independent 2HG production in HTB-126and MDA-MB-231 breast carcinoma cells by measuring C-13 incorporation from 1-C-13-glutamine into citrate, malate, and 2HG. For HTB-126 cells, C-13-citrate, C-13-malate, and C-13-2-hydroxyglutarate were enriched by 2-, 5-, and 15-fold at 5 mM glucose (2-,2.5-, and 13-fold at 25 mM glucose), respectively, after 6 h. Such enrichment decreased by 6% with IDH1 silencing, but by 30-50% upon IDH2 silencing while cell respiration and ATP levels rose up to 150%. Unlike 2HG production RCG decline

Název v anglickém jazyce

Reductive carboxylation and 2-hydroxyglutarate formation by wild-type IDH2 in breast carcinoma cells

Popis výsledku anglicky

Mitochondrial NADPH-dependent isocitrate dehydrogenase, IDH2, and cytosolic IDH1, catalyze reductive carboxylation of 2-oxoglutarate. Both idh2 and idh1 monoallelic mutations are harbored in grade 2/3 gliomas, secondary glioblastomas and acute myeloid leukemia. Mutant IDH1/IDH2 enzymes were reported to form an oncometabolite R-2-hydroxyglutarate (2HG), further strengthening malignancy. We quantified CO2-dependent reductive carboxylation glutaminolysis (RCG) and CO2-independent 2HG production in HTB-126and MDA-MB-231 breast carcinoma cells by measuring C-13 incorporation from 1-C-13-glutamine into citrate, malate, and 2HG. For HTB-126 cells, C-13-citrate, C-13-malate, and C-13-2-hydroxyglutarate were enriched by 2-, 5-, and 15-fold at 5 mM glucose (2-,2.5-, and 13-fold at 25 mM glucose), respectively, after 6 h. Such enrichment decreased by 6% with IDH1 silencing, but by 30-50% upon IDH2 silencing while cell respiration and ATP levels rose up to 150%. Unlike 2HG production RCG decline

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

CE - Biochemie

OECD FORD obor

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Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

S - Specificky vyzkum na vysokych skolach

Rok uplatnění

2015

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

International Journal of Biochemistry and Cell Biology

ISSN

1357-2725

e-ISSN

—

Svazek periodika

65

Číslo periodika v rámci svazku

August

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

9

Strana od-do

125-133

Kód UT WoS článku

000358804400013

EID výsledku v databázi Scopus

2-s2.0-84930938063