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

Autor(es)

Costa, Tiago J. ; Wilson, Emily W. ; Fontes, Milene T. ; Pernomian, Laena ; Tostes, Rita C. ; Wenceslau, Camilla F. ; McCarthy, Cameron G.

• Tipo de documento: Artigo Científico
• Fonte: Clinical Science; v. 137, n. 22, p. 15-pg., 2023-11-01.

Resumo

O-Linked attachment of beta-N-acetylglucosamine (O-GlcNAc) on serine and threonine residues of nuclear, cytoplasmic, and mitochondrial proteins is a highly dynamic and ubiquitous post-translational modification that impacts the function, activity, subcellular localization, and stability of target proteins. Physiologically, acute O-GlcNAcylation serves primarily to modulate cellular signaling and transcription regulatory pathways in response to nutrients and stress. To date, thousands of proteins have been revealed to be O-GlcNAcylated and this number continues to grow as the technology for the detection of O-GlcNAc improves. The attachment of a single O-GlcNAc is catalyzed by the enzyme O-GlcNAc transferase (OGT), and their removal is catalyzed by O-GlcNAcase (OGA). O-GlcNAcylation is regulated by the metabolism of glucose via the hexosamine biosynthesis pathway, and the metabolic abnormalities associated with pathophysiological conditions are all associ-ated with increased flux through this pathway and elevate O-GlcNAc levels. While chronic O-GlcNAcylation is well associated with cardiovascular dysfunction, only until recently, and with genetically modified animals, has O-GlcNAcylation as a contributing mechanism of cardiovascular disease emerged. This review will address and critically evaluate the current literature on the role of O-GlcNAcylation in vascular physiology, with a view that this pathway can offer novel targets for the treatment and prevention of cardiovascular diseases. (AU)

• Processo FAPESP: 13/08216-2 - CPDI - Centro de Pesquisa em Doenças Inflamatórias
• Beneficiário: Fernando de Queiroz Cunha
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
• Processo FAPESP: 19/26374-0 - Como o sexo e o estrógeno afetam a via da O-GlcNAc? Uma abordagem proteômica
• Beneficiário: Tiago Januário da Costa
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Pós-Doutorado