Methylglyoxal and high glucose inhibit VEGFR2 phosphorylation at specific tyrosine residues
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Fabian Betting
and
Gottfried Martin
Abstract
Diabetes is characterized by hyperglycemia and a significant risk of vascular complications. Vascular endothelial growth factor (VEGF) and its main receptor VEGFR2 (KDR), which is highly expressed in vascular endothelial cells, are essential mediators of vascular maintenance and angiogenesis. During glycolysis after high calorie food intake, methylglyoxal (MGO) is formed and MGO blood levels are elevated in diabetes. MGO reacts with arginine residues to generate MG-H1 or with lysine residues to carboxyethyl lysine which are common components of advanced glycation end-products. Therefore, the question arises whether hyperglycemic conditions affect VEGF signaling via a ligand-independent direct modification of signaling components. As a first step, the effect of MGO on VEGFR2 activation was investigated in cultured endothelial cells from human umbilical vein by determination of VEGFR2 phosphorylation at selected tyrosine residues by ELISA and immunoblotting using phospho-specific antibodies. Phosphorylation of VEGFR2-Y996, VEGFR2-Y1054, or VEGFR2-Y1175 reached a maximum 5 min after stimulation of endothelial cells with VEGF. Phosphorylation was significantly inhibited by 100 µM MGO and to a lesser extent by high glucose treatment. 2,3-Pentanedione and glyoxal were investigated for comparison. In summary, VEGFR2 phosphorylation is sensitive to MGO or high glucose concentrations which may be relevant in the pathophysiology of microvascular disease in diabetes.
Acknowledgments
We thank Marc Guder and Sophie Krüger for excellent technical assistance. FB was supported by a fellowship provided by the “Freunde der Universitäts-Augenklinik Freiburg” society.
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Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
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Research funding: None declared.
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Conflict of interest statement: The authors declare no conflicts of interest regarding this article.
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Articles in the same Issue
- Frontmatter
- Research Articles
- Synthesis, characterization, molecular docking, dynamics simulations, and in silico absorption, distribution, metabolism, and excretion (ADME) studies of new thiazolylhydrazone derivatives as butyrylcholinesterase inhibitors
- Study on the synthesis and structure-activity relationship of 1,2,3-triazoles against toxic activities of Bothrops jararaca venom
- In-silico elucidation reveals potential phytochemicals against angiotensin-converting enzyme 2 (ACE-2) receptor to fight coronavirus disease 2019 (COVID-19)
- Comparative study of phenolic profile, antioxidant and antimicrobial activities of aqueous extract of white and green tea
- Methylglyoxal and high glucose inhibit VEGFR2 phosphorylation at specific tyrosine residues
- Antidepressant alkaloids from the rhizomes of Corydalis decumbens
- Synthesis of new derivatives containing pyridine, investigation of MAO inhibitory activities and molecular docking studies
- Rapid Communications
- Chemical composition and bioactivities of Magnolia candollii H.Keng essential oil
- Chemical composition and anticholinesterase activity of Lepisanthes rubiginosa (Roxb.) Leenh. essential oil
Articles in the same Issue
- Frontmatter
- Research Articles
- Synthesis, characterization, molecular docking, dynamics simulations, and in silico absorption, distribution, metabolism, and excretion (ADME) studies of new thiazolylhydrazone derivatives as butyrylcholinesterase inhibitors
- Study on the synthesis and structure-activity relationship of 1,2,3-triazoles against toxic activities of Bothrops jararaca venom
- In-silico elucidation reveals potential phytochemicals against angiotensin-converting enzyme 2 (ACE-2) receptor to fight coronavirus disease 2019 (COVID-19)
- Comparative study of phenolic profile, antioxidant and antimicrobial activities of aqueous extract of white and green tea
- Methylglyoxal and high glucose inhibit VEGFR2 phosphorylation at specific tyrosine residues
- Antidepressant alkaloids from the rhizomes of Corydalis decumbens
- Synthesis of new derivatives containing pyridine, investigation of MAO inhibitory activities and molecular docking studies
- Rapid Communications
- Chemical composition and bioactivities of Magnolia candollii H.Keng essential oil
- Chemical composition and anticholinesterase activity of Lepisanthes rubiginosa (Roxb.) Leenh. essential oil
