O-GlcNAc as ammonia-induced glycosylation during the development of hyperammonemia.

Abstract

Hyperammonemia is a key pathological feature of hepatic encephalopathy (HE), yet its associated protein glycosylation remains incompletely understood. Here, we used whole mouse brain tissues from a hyperammonemia mouse model and astrocytes to conduct a comprehensive analysis of glycosylation changes and the corresponding enzyme associated with ammonia. The upregulation of O-linked N-acetylglucosamine (O-GlcNAc), mediated by O-GlcNAc transferase, was identified as a response to ammonia stimulation in astrocytes through a mechanism independent of glutamine synthesis and NADPH oxidase. These findings identify O-GlcNAc as an ammonia-sensitive post-translational modification that is associated with hyperammonemia. This study provides new insights into the molecular mechanisms of HE and suggests the potential role of O-GlcNAc as a therapeutic target warranting further investigation.