TY - JOUR
T1 - Increased vascular O-GlcNAcylation augments reactivity to constrictor stimuli - Vasoactive Peptide Symposium
AU - Lima, Victor V.
AU - Giachini, Fernanda R.C.
AU - Carneiro, Fernando S.
AU - Carneiro, Zidonia N.
AU - Fortes, Zuleica B.
AU - Carvalho, Maria Helena C.
AU - Webb, R. Clinton
AU - Tostes, Rita C.
N1 - Copyright:
Copyright 2011 Elsevier B.V., All rights reserved.
PY - 2008/11
Y1 - 2008/11
N2 - O-linked N-acetylglucosaminylation (O-GlcNAcylation) plays a role in many aspects of protein function. Whereas elevated O-GlcNAc levels contribute to diabetes-related end-organ damage, O-GlcNAcylation is also physiologically important. Because proteins that play a role in vascular tone regulation can be O-GlcNAcylated, we hypothesized that O-GlcNAcylation increases vascular reactivity to constrictor stimuli. Aortas from male Sprague-Dawley rats and C57BL/6 mice were incubated for 24 hours with vehicle or PugNAc (O-GlcNAcase inhibitor, 100 μM). PugNAc incubation significantly increased O-GlcNAc proteins, as determined by Western blot. PugNAc also increased vascular contractions to phenylephrine and serotonin, an effect not observed in the presence of Nω-nitro-L-arginine methyl ester or in endothelium-denuded vessels. Acetylcholine-induced relaxation, but not that to sodium nitroprusside, was decreased by PugNAc treatment, an effect accompanied by decreased levels of phosphorylated endothelial nitric oxide synthase (eNOS)Ser-1177 and AktSer-473. Augmented O-GlcNAcylation increases vascular reactivity to constrictor stimuli, possibly due to its effects on eNOS expression and activity, reinforcing the concept that O-GlcNAcylation modulates vascular reactivity and may play a role in pathological conditions associated with abnormal vascular function.
AB - O-linked N-acetylglucosaminylation (O-GlcNAcylation) plays a role in many aspects of protein function. Whereas elevated O-GlcNAc levels contribute to diabetes-related end-organ damage, O-GlcNAcylation is also physiologically important. Because proteins that play a role in vascular tone regulation can be O-GlcNAcylated, we hypothesized that O-GlcNAcylation increases vascular reactivity to constrictor stimuli. Aortas from male Sprague-Dawley rats and C57BL/6 mice were incubated for 24 hours with vehicle or PugNAc (O-GlcNAcase inhibitor, 100 μM). PugNAc incubation significantly increased O-GlcNAc proteins, as determined by Western blot. PugNAc also increased vascular contractions to phenylephrine and serotonin, an effect not observed in the presence of Nω-nitro-L-arginine methyl ester or in endothelium-denuded vessels. Acetylcholine-induced relaxation, but not that to sodium nitroprusside, was decreased by PugNAc treatment, an effect accompanied by decreased levels of phosphorylated endothelial nitric oxide synthase (eNOS)Ser-1177 and AktSer-473. Augmented O-GlcNAcylation increases vascular reactivity to constrictor stimuli, possibly due to its effects on eNOS expression and activity, reinforcing the concept that O-GlcNAcylation modulates vascular reactivity and may play a role in pathological conditions associated with abnormal vascular function.
KW - PugNAc
KW - eNOS
KW - phosphoinositide-3 kinase
KW - potassium chloride
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U2 - 10.1016/j.jash.2008.06.001
DO - 10.1016/j.jash.2008.06.001
M3 - Article
C2 - 19884969
AN - SCOPUS:57149117122
SN - 1933-1711
VL - 2
SP - 410
EP - 417
JO - Journal of the American Society of Hypertension
JF - Journal of the American Society of Hypertension
IS - 6
ER -