The Role of O-GlcNAcylation for Protection against Ischemia-Reperfusion Injury

Abstract

Ischemia reperfusion injury (IR injury) associated with ischemic heart disease contributes significantly to morbidity and mortality. O-linked β-N-acetylglucosamine (O-GlcNAc) is a dynamic posttranslational modification that plays an important role in numerous biological processes, both in normal cell functions and disease. O-GlcNAc increases in response to stress. This increase mediates stress tolerance and cell survival, and is protective. Increasing O-GlcNAc is protective against IR injury. Experimental cellular and animal models, and also human studies, have demonstrated that protection against IR injury by ischemic preconditioning, and the more clinically applicable remote ischemic preconditioning, is associated with increases in O-GlcNAc levels. In this review we discuss how the principal mechanisms underlying tissue protection against IR injury and the associated immediate elevation of O-GlcNAc may involve attenuation of calcium overload, attenuation of mitochondrial permeability transition pore opening, reduction of endoplasmic reticulum stress, modification of inflammatory and heat shock responses, and interference with established cardioprotective pathways. O-GlcNAcylation seems to be an inherent adaptive cytoprotective response to IR injury that is activated by mechanical conditioning strategies.

O ‐GlcNAcylation modulates HBV replication through regulating cellular autophagy at multiple levels

“…[45][46][47] However, other studies reported that O-GlcNAcylation of Akt positively modulates Akt activity. [48][49][50][51] In the present study, we found that Akt and mTOR are O-GlcNAcylated proteins in hepatoma cells. Akt/mTOR signaling pathway is known to negatively regulate HBV replication.…”

Cardiomyocyte Senescence and Cellular Communications Within Myocardial Microenvironments

“…Uridine diphosphate-N-acetylglucosamine (UDP-GlcNAc) is produced and used as the substrate of O-linked-GlcNAc transferase (OGT), which catalyzes the O-GlcNAcylation (O-GlcNAc) of proteins (48). Protein O-GlcNAcylation plays an essential role as a protective response in cardiomyocyte senescence via reducing calcium overload, mitochondrial permeability transition pore opening, ER stress, modification of inflammatory and heat shock responses (49). Of note, the cardiac protective effects of increasing O-GlcNAc levels have been emphasized in many pathologic conditions, including ischemic injury (50,51).…”

Glucosamine and O-GlcNAcylation: a novel immunometabolic therapeutic target for OA and chronic, low-grade systemic inflammation?

“…Experimental cardiac ischaemia/ reperfusion models showed that acute increases in protein O-GlcNAcylation induced by GlcN or glutamine correlated with a better functional recovery, while similar conclusions were obtained with the more clinically applicable remote ischaemic preconditioning. 29 In contrast to the benefit in acute and transient elevations, chronic increments or decreases in the levels of O-GlcNAcylated proteins have been associated with the pathogenesis of degenerative diseases such as Alzheimer's and Parkinson's, cancer, diabetes and Glucose enters the cell and is phosphorylated and then converted to fructose-6-phosphate. This product is then oxidised through glycolysis, and 3%-5% of it is converted to glucosamine-6-phosphate (GlcN-6P) by the limiting enzyme of this pathway, glutamine:fructose-6-phosphate-amidotransferase (GFAT), that transfers the amine group from the amino acid pool.…”