European Journal of Medical Research (Mar 2024)

O-GlcNAcylation: a pro-survival response to acute stress in the cardiovascular and central nervous systems

  • Qiu Xue,
  • Shengtao Ji,
  • Hui Xu,
  • Shu Yu

DOI
https://doi.org/10.1186/s40001-024-01773-z
Journal volume & issue
Vol. 29, no. 1
pp. 1 – 15

Abstract

Read online

Abstract O-GlcNAcylation is a unique monosaccharide modification that is ubiquitously present in numerous nucleoplasmic and mitochondrial proteins. The hexosamine biosynthesis pathway (HBP), which is a key branch of glycolysis, provides the unique sugar donor UDP-GlcNAc for the O-GlcNAc modification. Thus, HBP/O-GlcNAcylation can act as a nutrient sensor to perceive changes in nutrient levels and trigger O-GlcNAc modifications of functional proteins in cellular (patho-)physiology, thereby regulating diverse metabolic processes. An imbalance in O-GlcNAcylation has been shown to be a pathogenic contributor to dysfunction in metabolic diseases, including type 2 diabetes, cancer, and neurodegeneration. However, under acute stress conditions, protein O-GlcNAc modification exhibits rapid and transient upregulation, which is strongly correlated with stress tolerance and cell survival. In this context, we discuss the metabolic, pharmacological and genetic modulation of HBP/O-GlcNAc modification in the biological system, the beneficial role of O-GlcNAcylation in regulating stress tolerance for cardioprotection, and neuroprotection, which is a novel and rapidly growing field. Current evidence suggests that transient activation of the O-GlcNAc modification represents a potent pro-survival signalling pathway and may provide a promising strategy for stress-related disorder therapy.

Keywords