Increased vascular O-GlcNAcylation augments reactivity to constrictor stimuli — Vasoactive Peptide Symposium
Abstract 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 regu...
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Published in | Journal of the American Society of Hypertension Vol. 2; no. 6; pp. 410 - 417 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
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01.11.2008
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Abstract | Abstract 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. |
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AbstractList | 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.BACKGROUNDO-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 h with vehicle or PugNAc (O-GlcNAcase inhibitor, 100muM). 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 L-NAME 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 eNOS(Ser-1177) and Akt(Ser-473).METHODS AND RESULTSAortas from male Sprague-Dawley rats and C57BL/6 mice were incubated for 24 h with vehicle or PugNAc (O-GlcNAcase inhibitor, 100muM). 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 L-NAME 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 eNOS(Ser-1177) and Akt(Ser-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.CONCLUSIONAugmented 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. 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 h with vehicle or PugNAc (O-GlcNAcase inhibitor, 100muM). 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 L-NAME 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 eNOS(Ser-1177) and Akt(Ser-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. Abstract 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. |
Author | Webb, R. Clinton, PhD Carneiro, Zidonia N Lima, Victor V Giachini, Fernanda R.C., MSc Carvalho, Maria Helena C., PhD Carneiro, Fernando S., MSc Fortes, Zuleica B., PhD Tostes, Rita C., PhD |
AuthorAffiliation | 1 Department of Physiology, Medical College of Georgia, Augusta, GA, 30912-3000, USA 2 Department of Pharmacology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, SP, 05508-900, Brazil |
AuthorAffiliation_xml | – name: 2 Department of Pharmacology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, SP, 05508-900, Brazil – name: 1 Department of Physiology, Medical College of Georgia, Augusta, GA, 30912-3000, USA |
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Keywords | potassium chloride eNOS PugNAc phosphoinositide-3 kinase vascular reactivity O-Linked N-acetylglucosaminylation (O-GlcNAc) |
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Snippet | Abstract O-linked N-acetylglucosaminylation (O-GlcNAcylation) plays a role in many aspects of protein function. Whereas elevated O-GlcNAc levels contribute to... O-Linked N-acetylglucosaminylation (O-GlcNAcylation) plays a role in many aspects of protein function. Whereas elevated O-GlcNAc levels contribute to diabetes... |
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StartPage | 410 |
SubjectTerms | Cardiovascular |
Title | Increased vascular O-GlcNAcylation augments reactivity to constrictor stimuli — Vasoactive Peptide Symposium |
URI | https://www.clinicalkey.es/playcontent/1-s2.0-S1933171108001290 https://www.ncbi.nlm.nih.gov/pubmed/19884969 https://www.proquest.com/docview/733817305 https://pubmed.ncbi.nlm.nih.gov/PMC2630260 |
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