The O-GlcNAc dichotomy: when does adaptation become pathological?

Tiago J Costa1,2,3, Emily W Wilson1,2, Milene T Fontes1,2,3

  • 1Cardiovascular Translational Research Center, University of South Carolina School of Medicine-Columbia, SC, U.S.A.

Insights

O-Linked N-acetylglucosamine (O-GlcNAc) is a dynamic protein modification impacting cellular functions. Chronic O-GlcNAcylation contributes to cardiovascular disease, offering potential therapeutic targets.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Physiology

Background:

  • O-Linked N-acetylglucosamine (O-GlcNAc) is a dynamic post-translational modification affecting nuclear, cytoplasmic, and mitochondrial proteins.
  • O-GlcNAcylation modulates cellular signaling and transcription in response to nutrients and stress, with thousands of proteins identified as targets.
  • This modification is regulated by glucose metabolism via the hexosamine biosynthesis pathway, and its dysregulation is linked to metabolic abnormalities.

Approach:

  • This review critically evaluates current literature on O-GlcNAcylation in vascular physiology.
  • Focuses on the role of O-GlcNAcylation as a contributing mechanism in cardiovascular disease.
  • Examines findings from genetically modified animal models to understand O-GlcNAcylation's impact.

Key Points:

  • O-GlcNAcylation influences protein function, activity, localization, and stability.
  • Acute O-GlcNAcylation is crucial for cellular signaling and transcription.
  • Chronic O-GlcNAcylation is increasingly recognized as a factor in cardiovascular dysfunction.

Conclusions:

  • O-GlcNAcylation, regulated by glucose metabolism, plays a significant role in vascular physiology.
  • Elevated O-GlcNAc levels due to metabolic abnormalities are linked to cardiovascular disease.
  • The O-GlcNAcylation pathway presents novel therapeutic targets for cardiovascular disease prevention and treatment.

Related Concept Videos

Proteoglycans01:05

Proteoglycans

Glycans, a class of complex heterogeneous molecules, can be covalently attached to proteins to form glycosylated proteins that regulate various physiological and pathological processes. Glycosylated proteins or glycoproteins comprise N-linked and O-linked oligosaccharides. O-glycosylation is the most common type of protein glycosylation. Here, glycans attach to the oxygen atom of the hydroxyl groups of Serine or Threonine residues. O-linked glycosylation occurs later in protein processing,...
3.9K
Oligosaccharide Assembly01:24

Oligosaccharide Assembly

Protein glycosylation starts in the ER lumen and continues in the Golgi apparatus. Glycosyltransferases catalyze the addition of sugar molecules or glycosylation of proteins. Usually, these enzymes add sugars to the hydroxyl groups of selected serine or threonine residues to form O-linked glycans or the amino groups of asparagine residues to form N-linked glycans. Different positions on the same polypeptide chain can contain differently linked glycans.
Multiple sugar molecules that may or may...
2.9K
Ligand-Gated Ion Channel Receptor: Gating Mechanism01:30

Ligand-Gated Ion Channel Receptor: Gating Mechanism

Ligand-gated ion channels are transmembrane proteins that play a vital role in intercellular communication and functions of the nervous system. They allow the influx of ions across the membrane once the neurotransmitter binds, allowing the subsequent transmission of electrical excitation across the neurons. Other ligand-gated ion channels, like the γ-aminobutyric acid (GABA) receptor, permit anions like chloride into the cells on the binding of the GABA molecule. Their entry into the cell...
2.3K
Protein Glycosylation01:25

Protein Glycosylation

Glycosylation, the most common post-translational modification for proteins, serves diverse functions. Adding sugars to proteins makes the proteins more resistant to proteolytic digestion. Glycosylated proteins can act as markers and receptors to promote cell-cell adhesion. Additionally, they have many essential quality control functions in the cell, such as correct protein folding and facilitating transport of misfolded proteins to the cytosol, which can be degraded.
Glycosylation occurs in...
7.0K
Overview of Carbohydrate Metabolism01:19

Overview of Carbohydrate Metabolism

Carbohydrate metabolism is a fundamental biochemical process that ensures a constant supply of energy to living cells. The most important carbohydrate is glucose, which can be broken down via glycolysis to enter into the Krebs cycle and eventually lead to the production of ATP through oxidative phosphorylation.
Glucose transport into cells is facilitated by a family of transport proteins called GLUT (Glucose Transporters). GLUT4 is the primary glucose transporter for insulin-stimulated glucose...
1.1K
Neuroplasticity01:01

Neuroplasticity

Neuroplasticity reflects the brain's remarkable capacity to adapt and evolve, responding dynamically to learning, experiences, or injury by reorganizing its neural circuitry. This reorganization involves creating new neural connections and refining old ones through a series of biological processes that contribute to the brain's lifelong development and adaptability.
370