ArticleCardiovascular diabetology2013
Methylglyoxal modulates endothelial nitric oxide synthase-associated functions in EA.hy926 endothelial cells.
Article in Cardiovascular diabetology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 35 citations in OpenAlex.
- Role of Glycolysis and Nitric Oxide Pathway Crosstalk in Macrophages in Atherosclerosis.Current medicinal chemistry · 2026Review
- Acacetin reduces endoplasmic reticulum stress through the P-eNOS/PERK signaling pathway to attenuate MGO-induced vascular endothelial cell dysfunction.FEBS open bio · 2025Article
- Methylglyoxal in Cardiometabolic Disorders: Routes Leading to Pathology Counterbalanced by Treatment Strategies.Molecules (Basel, Switzerland) · 2023Review
- Pancreatic steatosis and metabolic pancreatic disease: a new entity?Internal and emergency medicine · 2023Review
- L-Arginine in diabetes: clinical and preclinical evidence.Cardiovascular diabetology · 2023Review
- Novel Role of GPR35 (G-Protein-Coupled Receptor 35) in the Regulation of Endothelial Cell Function and Blood Pressure.Hypertension (Dallas, Tex. : 1979) · 2021Article
- UnripeAntioxidants (Basel, Switzerland) · 2021Article
- Vascular endothelial dysfunction, a major mediator in diabetic cardiomyopathy.Acta pharmacologica Sinica · 2019Review
- Glyoxalases in Urological Malignancies.International journal of molecular sciences · 2018Review
- Endothelial Cell Metabolism.Physiological reviews · 2018Review
- Loss of Glyoxalase 1 Induces Compensatory Mechanism to Achieve Dicarbonyl Detoxification in Mammalian Schwann Cells.The Journal of biological chemistry · 2017Article
- Association of secreted frizzled-related protein 4 (SFRP4) with type 2 diabetes in patients with stable coronary artery disease.Cardiovascular diabetology · 2014Article
- Endothelial Na+/H+ exchanger NHE1 participates in redox-sensitive leukocyte recruitment triggered by methylglyoxal.Cardiovascular diabetology · 2014Article
- AGEs breaking and antioxidant treatment improves endothelium-dependent dilation without effect on flow-mediated remodeling of resistance arteries in old Zucker diabetic rats.Cardiovascular diabetology · 2014Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundIncreased levels of the sugar metabolite methylglyoxal (MG) in vivo were shown to participate in the pathophysiology of vascular complications in diabetes. Alterations of endothelial nitric oxide synthase (eNOS) activity by hypophosphorylation of the enzyme and enhanced monomerization are found in the diabetic milieu, and the regulation of this still remains undefined. Using various pharmacological approaches, we elucidate putative mechanisms by which MG modulates eNOS-associated functions of MG-stimulated superoxide O₂•⁻ production, phosphorylation status and eNOS uncoupling in EA.hy926 human endothelial cells.
methodsIn cultured EA.hy926 endothelial cells, the effects of MG treatment, tetrahydrobiopterin (BH4; 100 μM) and sepiapterin (20 μM) supplementation, NOS inhibition by N(G)-nitro-L-arginine methyl ester (L-NAME; 50 μM), and inhibition of peroxynitrite (ONOO⁻) formation (300 μM Tempol plus 50 μM L-NAME) on eNOS dimer/monomer ratios, Ser-1177 eNOS phosphorylation and 3-nitrotyrosine (3NT) abundance were quantified using immunoblotting. O₂•⁻-dependent fluorescence was determined using a commercially available kit and tissue biopterin levels were measured by fluorometric HPLC analysis.
resultsIn EA.hy926 cells, MG treatment significantly enhanced O₂•⁻ generation and 3NT expression and reduced Ser-1177 eNOS phosphorylation, eNOS dimer/monomer ratio and cellular biopterin levels indicative of eNOS uncoupling. These effects were significantly mitigated by administration of BH4, sepiapterin and suppression of ONOO⁻ formation. L-NAME treatment significantly blunted eNOS-derived O₂•⁻ generation but did not modify eNOS phosphorylation or monomerization.
conclusionMG triggers eNOS uncoupling and hypophosphorylation in EA.hy926 endothelial cells associated with O₂•⁻ generation and biopterin depletion. The observed effects of the glycolysis metabolite MG presumably account, at least in part, for endothelial dysfunction in diabetes.
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