Metabolic reprogramming contributes to radioprotection by protein kinase Cδ.

ABSTRACT: Loss of protein kinase Cδ (PKCδ) activity renders cells resistant to DNA damaging agents, including irradiation; however, the mechanism(s) underlying resistance is poorly understood. Here, we have asked if metabolic reprogramming by PKCδ contributes to radioprotection. Analysis of global metabolomics showed that depletion of PKCδ affects metabolic pathways that control energy production and antioxidant, nucleotide, and amino acid biosynthesis. Increased NADPH and nucleotide production in PKCδ-depleted cells is associated with upregulation of the pentose phosphate pathway (PPP) as evidenced by increased activation of G6PD and an increase in the nucleotide precursor, 5-phosphoribosyl-1-pyrophosphate. Stable isotope tracing with U-[¹³C₆] glucose showed reduced utilizatio

SUBMITTER: Ohm AM 

PROVIDER: S-EPMC10519828 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature