Uric acid inhibition of dipeptidyl peptidase IV in vitro is dependent on the intracellular formation of triuret
| Autor: | Wai-Yan Chan, Robert McKenna, Richard J. Johnson, Laura Sautina, John F. Domsic, Mark S. Segal, Anna Schuler, Elaine Beem, Rajesh Mohandas |
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| Rok vydání: | 2014 |
| Předmět: |
Models
Molecular Metalloporphyrins Dipeptidyl Peptidase 4 Cell Pharmacology Biology Endothelial progenitor cell Article Antioxidants Dipeptidyl peptidase chemistry.chemical_compound Human Umbilical Vein Endothelial Cells medicine Humans Urea Enzyme Inhibitors Dipeptidyl peptidase-4 nutritional and metabolic diseases Free Radical Scavengers Cell Biology Oxidants Recombinant Proteins Hypochlorous Acid Uric Acid medicine.anatomical_structure chemistry Biochemistry Uric acid Triuret Peroxynitrite Intracellular |
| Zdroj: | Experimental Cell Research. 326:136-142 |
| ISSN: | 0014-4827 |
| DOI: | 10.1016/j.yexcr.2014.05.025 |
| Popis: | Uric acid affects endothelial and adipose cell function and has been linked to diseases such as hypertension, metabolic syndrome, and cardiovascular disease. Interestingly uric acid has been shown to increase endothelial progenitor cell (EPC) mobilization, a potential mechanism to repair endothelial injury. Since EPC mobilization is dependent on activity of the enzyme CD26/dipeptidyl peptidase (DPP)IV, we examined the effect uric acid will have on CD26/DPPIV activity. Uric acid inhibited the CD26/DPPIV associated with human umbilical vein endothelial cells but not human recombinant (hr) CD26/DPPIV. However, triuret, a product of uric acid and peroxynitrite, could inhibit cell associated and hrCD26/DPPIV. Increasing or decreasing intracellular peroxynitrite levels enhanced or decreased the ability of uric acid to inhibit cell associated CD26/DPPIV, respectively. Finally, protein modeling demonstrates how triuret can act as a small molecule inhibitor of CD26/DPPIV activity. This is the first time that uric acid or a uric acid reaction product has been shown to affect enzymatic activity and suggests a novel avenue of research in the role of uric acid in the development of clinically important diseases. |
| Databáze: | OpenAIRE |
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