Multitranscript analysis reveals an effect of 2-deoxy-d-glucose on gene expression linked to unfolded protein response and integrated stress response in primary human monocytes and monocyte-derived macrophages.
Level 5 - mechanism / opinion, no new human data
In vitro bench study and bioinformatics analysis of RNA-seq datasets
PubMed 37290716 · doi:10.1016/j.bbagen.2023.130397
What was done
Bioinformatics re-analysis was conducted on previously reported RNA-seq datasets to detect differentially expressed genes (DEGs) in primary human monocytes and monocyte-derived macrophages (MDMs) treated with 2-deoxy-d-glucose (2-DG). RT-qPCR was then performed on cultured MDMs to verify the sequencing results.
What was found
Analysis identified 95 common DEGs in monocytes and MDMs exposed to 2-DG, consisting of 74 up-regulated and 21 down-regulated genes. Altered transcripts mapped to the integrated stress response and unfolded protein response (GRP78/BiP, PERK, ATF4, CHOP, GADD34, IRE1α, XBP1, SESN2, ASNS, PHGDH), the hexosamine biosynthetic pathway (GFAT1, GNA1, PGM3, UAP1), and mannose metabolism (GMPPA and GMPPB). Exact fold-changes, statistical thresholds, and quantitative RT-qPCR values were not reported in the abstract.
Why it matters
The findings characterize the specific gene expression program triggered by 2-DG in primary human myeloid cells, highlighting that 2-DG acts as a broad stress inducer altering proteostasis and metabolic pathways beyond simple glycolytic inhibition.
Limits
The study is limited to in vitro transcriptional profiling and secondary data analysis. Sample sizes (number of biological donors), treatment concentrations, exposure durations, and protein-level or functional metabolic validations were not specified in the abstract.
Cited by
- supports 2-deoxyglucose increases protein chaperones, including glucose-regulated protein 78 (GRP78).