TY - JOUR
T1 - O-GlcNAcylation
T2 - a novel post-translational mechanism to alter vascular cellular signaling in health and disease: focus on hypertension
AU - Lima, Victor V.
AU - Rigsby, Christiné S.
AU - Hardy, David M.
AU - Webb, R. Clinton
AU - Tostes, Rita C.
N1 - Funding Information:
Supported by the National Institutes of Health and Cardiovascular Discovery Institute, EUA and CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior), Brazil.
PY - 2009/11
Y1 - 2009/11
N2 - 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.
AB - 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.
KW - O-Linked ß-N-acetylglucosaminylation (O-GlcNAc)
KW - protein kinases
KW - vascular (dys)function
UR - http://www.scopus.com/inward/record.url?scp=70549093288&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=70549093288&partnerID=8YFLogxK
U2 - 10.1016/j.jash.2009.09.004
DO - 10.1016/j.jash.2009.09.004
M3 - Review article
C2 - 20409980
AN - SCOPUS:70549093288
SN - 1933-1711
VL - 3
SP - 374
EP - 387
JO - Journal of the American Society of Hypertension
JF - Journal of the American Society of Hypertension
IS - 6
ER -