O-GlcNAcylation: a novel post-translational mechanism to alter vascular cellular signaling in health and disease: focus on hypertension

Victor V. Lima, Christiné S. Rigsby, David M. Hardy, R. Clinton Webb, Rita C. Tostes

Research output: Contribution to journalReview article

25 Scopus citations

Abstract

O-Linked attachment of β-N-acetyl-glucosamine (O-GlcNAc) on serine and threonine residues of nuclear and cytoplasmic proteins is a highly dynamic posttranslational modification that plays a key role in signal transduction pathways. Preliminary data show that O-GlcNAcylation may represent a key regulatory mechanism in the vasculature, modulating contractile and relaxant responses. Proteins with an important role in vascular function, such as endothelial nitric oxide synthase, sarcoplasmic reticulum Ca2+-ATPase, protein kinase C, mitogen-activated protein kinases, and proteins involved in cytoskeleton regulation and microtubule assembly are targets for O-GlcNAcylation, indicating that this posttranslational modification may play an important role in vascular reactivity. Here, we will focus on a few specific pathways that contribute to vascular function and cardiovascular disease-associated vascular dysfunction, and the implications of their modification by O-GlcNAc. New chemical tools have been developed to detect and study O-GlcNAcylation, including inhibitors of O-GlcNAc enzymes, chemoenzymatic tagging methods, and quantitative proteomics strategies; these will also be briefly addressed. An exciting challenge in the future will be to better understand the cellular dynamics of this posttranslational modification, as well as the signaling pathways and mechanisms by which O-GlcNAc is regulated on specific proteins in the vasculature in health and disease.

Original languageEnglish (US)
Pages (from-to)374-387
Number of pages14
JournalJournal of the American Society of Hypertension
Volume3
Issue number6
DOIs
StatePublished - Nov 2009

Keywords

  • O-Linked ß-N-acetylglucosaminylation (O-GlcNAc)
  • protein kinases
  • vascular (dys)function

ASJC Scopus subject areas

  • Internal Medicine
  • Cardiology and Cardiovascular Medicine

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