Speaker: Dr. Ann Wells from the Jackson Laboratory.
Title: 2-Deoxyglucose Inhibits N-glycosylation and Glycolysis Modulating Biochemical Pathways in a Tissue-Specific Manner in C57BL6/J Mice
Abstract: Assessing the systemic effects of 2-deoxyglucose (2DG) is important in order to understand how 2DG alters gene function across tissues. 2DG disrupts glycolysis through competitive inhibition of glucose-6-phosphate. This results in an accumulation of 2DG-6-phosphate in the cell. Additionally, 2DG disrupts n-glycosylation through competition with mannose resulting in misfolded proteins and leading to endoplasmic reticulum stress. 2DG has been studied as a potential therapeutic treatment for cancer and epilepsy. Most recently, 2DG has been shown to attenuate systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Currently, 2DG is being used to treat severe acute respiratory syndrome- coronavirus 2 (SARS-CoV-2) in India. To elucidate how 2DG modulates pathways systemically, independent of disease, C57BL6/J were treated orally with 2DG, after which the transcriptional profiles of nine tissues (heart, hippocampus, hypothalamus, kidney, liver, prefrontal cortex, skeletal muscle, small intestine, and spleen) were analyzed using unsupervised clustering and weighted gene co-network analysis. Principal component analysis revealed that samples predominantly clustered by tissue. Six modules, one per tissue, were revealed to be affected by 2DG. Pathways and genes for each tissue module were unique with very little overlap. In the heart 2DG predominantly affected mitochondrial metabolism while, in the small intestine 2DG affected immunological pathways. These results show that 2DG has a systemic impact that varies across organs.
Sunday 3 November 2024
