Different Effects of RNAi-Mediated Downregulation or Chemical Inhibition of NAMPT in an Isogenic IDH Mutant and Wild-Type Glioma Cell Model.

ABSTRACT: The IDH1^R132H mutation in glioma results in the neoenzymatic function of IDH1, leading to the production of the oncometabolite 2-hydroxyglutarate (2-HG), alterations in energy metabolism and changes in the cellular redox household. Although shifts in the redox ratio NADPH/NADP⁺ were described, the consequences for the NAD⁺ synthesis pathways and potential therapeutic interventions were largely unexplored. Here, we describe the effects of heterozygous IDH1^R132H on the redox system in a CRISPR/Cas edited glioblastoma model and compare them with IDH1 wild-type (IDH1^wt) cells. Besides an increase in 2-HG and decrease in NADPH, we observed an increase in NAD⁺ in IDH1^R132H glioblastoma cells. RT-qPCR analysis revealed t

SUBMITTER: Clausing M 

PROVIDER: S-EPMC9143996 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature