O-GlcNAcylation dictates pyroptosis

Yue Lang; Jincheng Li; Leiliang Zhang

doi:10.3389/fimmu.2024.1513542

O-GlcNAcylation dictates pyroptosis

Front Immunol. 2024 Dec 17:15:1513542. doi: 10.3389/fimmu.2024.1513542. eCollection 2024.

Authors

Yue Lang^{1

2}, Jincheng Li², Leiliang Zhang^{1

2}

Affiliations

¹ Department of Clinical Laboratory Medicine, The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Jinan, Shandong, China.
² Department of Pathogen Biology, School of Clinical and Basic Medical Sciences, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China.

Abstract

O-GlcNAcylation is a dynamic post-translational modification involving the attachment of N-acetylglucosamine to serine and threonine residues. This review emphasizes its role in regulating the signaling pathways of pyroptosis. Specifically, the O-GlcNAcylation of GSDMD is linked to the modulation of pyroptosis, suggesting that enhancing O-GlcNAcylation of GSDMD could be crucial for improving hypoperfusion in sepsis. Additionally, GSDME, another member of the gasdermin family, facilitates macrophage pyroptosis through O-GlcNAcylation induced by high glucose levels in the context of periodontitis. The review also examines the effects of O-GlcNAcylation on the NLRP3 inflammasome and its regulators, including NEK7 and NF-κB. Overall, this review emphasizes the role of O-GlcNAcylation in the pathogenesis of conditions such as sepsis, periodontitis, and osteoarthritis, identifying potential therapeutic targets for managing inflammatory responses through its targeted modulation.

Keywords: GSDMD; GSDME; NLRP3; O-GlcNAcylation; pyroptosis.

Publication types

Review

MeSH terms

Acetylglucosamine / metabolism
Animals
Gasdermins
Humans
Inflammasomes* / metabolism
Intracellular Signaling Peptides and Proteins / metabolism
Macrophages / immunology
Macrophages / metabolism
NF-kappa B / metabolism
NIMA-Related Kinases / metabolism
NLR Family, Pyrin Domain-Containing 3 Protein / metabolism
Osteoarthritis / immunology
Osteoarthritis / metabolism
Osteoarthritis / pathology
Periodontitis / immunology
Periodontitis / metabolism
Phosphate-Binding Proteins* / metabolism
Protein Processing, Post-Translational*
Pyroptosis*
Sepsis / immunology
Sepsis / metabolism
Signal Transduction

Substances

Inflammasomes
Phosphate-Binding Proteins
GSDMD protein, human
NLR Family, Pyrin Domain-Containing 3 Protein
Acetylglucosamine
Intracellular Signaling Peptides and Proteins
NF-kappa B
NIMA-Related Kinases
NEK7 protein, human
Gasdermins

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by National Natural Science Foundation of China (82272306 and 82072270), Shandong Provincial Natural Science Foundation (ZR2024MH017), and Taishan Scholars Program (tstp20221142).