Moderate exercise attenuates caspase-3 activity, oxidative stress, and inhibits progression of diabetic renal disease indb/dbmice
| Autor: | Kumar Sharma, Sanjoy Ghosh, Ismail Laher, Andrew P. Mizisin, Stephen R. Dunn, Peter McCue, Farzad Moien-Afshari, C. B. Verchere, Lisa S. Ang, David J. Granville, Majid Khazaei |
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| Rok vydání: | 2009 |
| Předmět: |
Male
medicine.medical_specialty Physiology Down-Regulation Apoptosis Caspase 3 Kidney medicine.disease_cause Caspase 8 Nephropathy Diabetic nephropathy Mice chemistry.chemical_compound Bcl-2-associated X protein Internal medicine medicine Albuminuria Animals Diabetic Nephropathies bcl-2-Associated X Protein biology Superoxide Dismutase Tumor Necrosis Factor-alpha business.industry Nitrotyrosine Age Factors Articles medicine.disease Exercise Therapy Mitochondria Disease Models Animal Oxidative Stress Endocrinology medicine.anatomical_structure Diabetes Mellitus Type 2 Proto-Oncogene Proteins c-bcl-2 chemistry Disease Progression biology.protein business Oxidative stress |
| Zdroj: | American Journal of Physiology-Renal Physiology. 296:F700-F708 |
| ISSN: | 1522-1466 1931-857X |
| DOI: | 10.1152/ajprenal.90548.2008 |
| Popis: | Diabetic nephropathy, the leading cause of end-stage renal disease, is characterized by a proapoptotic and prooxidative environment. The mechanisms by which lifestyle interventions, such as exercise, benefit diabetic nephropathy are unknown. We hypothesized that exercise inhibits early diabetic nephropathy via attenuation of the mitochondrial apoptotic pathway and oxidative damage. Type 2 diabetic db/db and normoglycemic wild-type mice were exercised for an hour everyday at a moderate intensity for 7 wk, following which renal function, morphology, apoptotic signaling, and oxidative stress were evaluated. Exercise reduced body weight, albuminuria, and pathological glomerular expansion in db/db mice independent of hyperglycemic status. Changes in renal morphology were also related to reduced caspase-3 (main effector caspase in renal apoptosis), caspase-8 (main initiator caspase of the “extrinsic” pathway) activities, and TNF-α expression. A role for the mitochondrial apoptotic pathway was unlikely as both caspase-9 activity (initiator caspase of this pathway) and expression of regulatory proteins such as Bax and Bcl-2 were unchanged. Kidneys from db/db mice also produced higher levels of superoxides and had greater oxidative damage concurrent with downregulation of superoxide dismutase (SOD) 1 and 3. Interestingly, although exercise also increased superoxides, there was also upregulation of multiple SODs that likely inhibited lipid (hydroperoxides) and protein (carbonyls and nitrotyrosine) oxidation in db/db kidneys. In conclusion, exercise can inhibit progression of early diabetic nephropathy independent of hyperglycemia. Reductions in caspase-3 and caspase-8 activities, with parallel improvements in SOD expression and reduced oxidative damage, could underlie the beneficial effects of exercise in diabetic kidney disease. |
| Databáze: | OpenAIRE |
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