Ketohexokinase-Dependent Metabolism of Fructose Induces Proinflammatory Mediators in Proximal Tubular Cells
| Autor: | Richard J. Johnson, George N. Henderson, Loreto Gesualdo, Philip M. Scherer, Michael S. Gersch, Yuri Y. Sautin, Pietro Cirillo, Wei Mu, Kyung Mee Kim |
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| Rok vydání: | 2009 |
| Předmět: |
Male
medicine.medical_specialty Xanthine Dehydrogenase Fructose 1 6-bisphosphatase Fructose Transfection Cell Line Proinflammatory cytokine Fructokinases Kidney Tubules Proximal Rats Sprague-Dawley chemistry.chemical_compound Adenosine Triphosphate Internal medicine medicine Animals Humans RNA Messenger RNA Small Interfering Renal Insufficiency Chronic Chemokine CCL2 DNA Primers Metabolic Syndrome NADPH oxidase Base Sequence biology General Medicine Metabolism Rats Uric Acid Endocrinology chemistry Biochemistry Nephrology Fructolysis biology.protein Uric acid Inflammation Mediators Reactive Oxygen Species Oxidation-Reduction |
| Zdroj: | Journal of the American Society of Nephrology. 20:545-553 |
| ISSN: | 1046-6673 |
| Popis: | Increased consumption of fructose may play an important role in the epidemic of metabolic syndrome and may presage the development of diabetes, cardiovascular disease, and chronic kidney disease. Once in the cell, fructose is phosphorylated by ketohexokinase (KHK), leading to consumption of ATP, formation of AMP, and generation of uric acid through xanthine oxidoreductase (XOR). This study aimed to examine the direct effects of fructose in human kidney proximal tubular cells (HK-2) and whether they are mediated by the fructose metabolism via KHK. At a similar concentration to that observed in peripheral blood after a meal, fructose induced production of monocyte chemotactic protein 1 (MCP-1) and reactive oxygen species in HK-2 cells. Knockdown of KHK by stable transfection with small hairpin RNA demonstrated that these processes were KHK dependent. Several antioxidants, including specific inhibitors of NADPH oxidase and XOR, prevented MCP-1 secretion. We detected XOR mRNA in HK-2 cells and confirmed its activity by identifying uric acid by mass spectrometry. Fructose increased intracellular uric acid, and uric acid induced production of MCP-1 as well. In summary, postprandial concentrations of fructose stimulate redox- and urate-dependent inflammatory mediators in proximal tubular cells. |
| Databáze: | OpenAIRE |
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