Major
Microbiology
Advisor
Townson, David, H
Advisor Department
Animal and Veterinary Science
Date
5-2025
Keywords
O-GlcNAcylation; Mitochondrial biomass; BPAECs; Diabetes; Endothelial cells
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-Share Alike 4.0 License.
Abstract
O-GlcNAcylation, a post-translational modification of proteins with sugar molecules, plays an important role in a variety of cellular processes, including energy production. Disrupted regulation of O-GlcNAcylation is associated with the pathology of diabetes and can lead to potential damage to the endothelial cells of blood vessels. The current study investigated the effect of manipulating O-GlcNAcylation on mitochondrial biomass in such endothelial cells. Briefly, bovine pulmonary aortic endothelial cells (BPAECs) were grown to confluency and then exposed to pharmaceutical agents that either impair (OSMI-1) or enhance (Thiamet-G) O-GlcNAcylation. Following 24 hours of treatment, the BPAECs were then stained with MitoTracker™ fluorescent green to visualize and measure mitochondrial biomass. The results indicated a significant decrease in mitochondrial biomass following the highest dose of OSMI-1 (P< 0.05, n=3 independent experiments) compared to control, suggesting that strong inhibition of O-GlcNAcylation damages endothelial cells via their mitochondria. Comparatively, mitochondrial biomass was unaffected (P>0.05) by Thiamet-G treatment. Collectively, these observations suggest that a certain level of O-GlcNAcylation is necessary to support mitochondrial homeostasis in endothelial cells and that disrupting this balance impairs their capacity to metabolically generate energy. This work offers insight into how glucose-driven protein modifications may affect mitochondrial dynamics in the onset of diabetes, which could guide future research into the minimization of vascular complications of the disease.