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Updated: May 20, 2026
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Published on: September 19, 2016
Acute O-GlcNAcylation prevents inflammation-induced vascular dysfunction.
Rob H P Hilgers1, Dongqi Xing, Kaizheng Gong
1Vascular Biology and Hypertension Program, Division of Cardiovascular Disease, Department of Medicine, University of Alabama, Birmingham, Alabama 35294-0007, USA.
Summary
Increasing protein O-linked N-acetyl-glucosamine (O-GlcNAcylation) protects against TNF-α-induced vascular dysfunction. Agents like d-glucosamine (d-GlcN) and Thiamet-G suppress inducible nitric oxide synthase (iNOS) expression, preventing damage.
Area of Science:
- Biochemistry
- Molecular Biology
- Cardiovascular Research
Background:
- Acute increases in cellular protein O-linked N-acetyl-glucosamine (O-GlcNAc) modification (O-GlcNAcylation) demonstrate protective effects in the heart and vasculature.
- Tumor necrosis factor-alpha (TNF-α) can induce oxidative stress and vascular dysfunction.
Purpose of the Study:
- To investigate whether d-glucosamine (d-GlcN) and Thiamet-G, agents that increase O-GlcNAcylation, inhibit TNF-α-induced oxidative stress and vascular dysfunction.
- To determine if these agents suppress inducible nitric oxide synthase (iNOS) expression as a mechanism of protection.
Main Methods:
- Rat aortic rings were pretreated with d-GlcN or Thiamet-G, followed by incubation with TNF-α.
- Arterial reactivity was assessed using a myograph.
- Protein O-GlcNAc levels, iNOS expression, and nitrotyrosylated proteins were analyzed.
Main Results:
- TNF-α induced hypocontractility and endothelial dysfunction in aortic rings.
- Pretreatment with d-GlcN or Thiamet-G suppressed TNF-α-induced vascular dysfunction and increased O-GlcNAcylation.
- Both agents attenuated the TNF-α-induced increase in iNOS expression and nitrotyrosylated proteins.
Conclusions:
- Acute increases in protein O-GlcNAcylation prevent TNF-α-induced vascular dysfunction.
- Suppression of inducible nitric oxide synthase (iNOS) expression is a key mechanism underlying this protective effect.
- d-GlcN and Thiamet-G show potential therapeutic value in mitigating inflammatory vascular damage.
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