Glycation of mitochondrial proteins from diabetic rat kidney is associated with excess superoxide formation
| Autor: | Vincent M. Monnier, Michael Kinter, Aylin M. Ozdemir, Miriam F. Weiss, Timothy S. Kern, Tiberiu G. Mustata, Luke I. Szweda, Michael Brownlee, Mariana G. Rosca |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Blood Glucose
Male medicine.medical_specialty Physiology Blotting Western Oxidative phosphorylation Mitochondrion Biology medicine.disease_cause Guanidines Oxidative Phosphorylation 2 4-Dinitrophenol Diabetes Mellitus Experimental Mitochondrial Proteins chemistry.chemical_compound Oxygen Consumption Glycation Multienzyme Complexes Superoxides Diabetes mellitus Internal medicine medicine Animals Diabetic Nephropathies Electrophoresis Gel Two-Dimensional NADH NADPH Oxidoreductases Superoxide Uncoupling Agents Fatty Acids medicine.disease Oxidants Pyruvaldehyde Mitochondria Rats Oxidative Stress Endocrinology Glucose chemistry Rats Inbred Lew Coenzyme Q – cytochrome c reductase Energy Metabolism Oxidation-Reduction Oxidative stress |
| Zdroj: | American journal of physiology. Renal physiology. 289(2) |
| ISSN: | 1931-857X |
| Popis: | Chronic hyperglycemia causes structural alterations of proteins through the Maillard reaction. In diabetes, methylglyoxal (MGO)-induced hydroimidazolones are the predominant modification. In contrast to acute hyperglycemia, mitochondrial respiration is depressed in chronic diabetes. To determine whether MGO-derived protein modifications result in abnormalities in mitochondrial bioenergetics and superoxide formation, proteomics and functional studies were performed in renal cortical mitochondria isolated from rats with 2, 6, and 12 mo of streptozotocin-induced diabetes. MGO-modified proteins belonged to the following two pathways: 1) oxidative phosphorylation and 2) fatty acid β-oxidation. Two of these proteins were identified as components of respiratory complex III, the major site of superoxide production in health and disease. Mitochondria from rats with diabetes exhibited a diminution of oxidative phosphorylation. A decrease in the respiratory complex III activity was significantly correlated with the quantity of MGO-derived hydroimidazolone present on mitochondrial proteins in both diabetic and control animals. In diabetes, isolated renal mitochondria produced significantly increased quantities of superoxide and showed evidence of oxidative damage. Administration of aminoguanidine improved mitochondrial respiration and complex III activity and decreased oxidative damage to mitochondrial proteins. Therefore, posttranslational modifications of mitochondrial proteins by MGO may represent pathogenic events leading to mitochondria-induced oxidative stress in the kidney in chronic diabetes. |
| Databáze: | OpenAIRE |
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