Coenzyme Q10 prevents GDP-sensitive mitochondrial uncoupling, glomerular hyperfiltration and proteinuria in kidneys from db/db mice as a model of type 2 diabetes

Autor: S.-B. Catrina, Peter Hansell, Fredrik Palm, Gustav Dallner, Kerstin Brismar, Stephanie Franzén, M. Friederich Persson
Rok vydání: 2012
Předmět:
Blood Glucose
medicine.medical_specialty
Ubiquinone
Endocrinology
Diabetes and Metabolism
Kidney Glomerulus
030209 endocrinology & metabolism
Type 2 diabetes
Mitochondrion
Biology
medicine.disease_cause
Guanosine Diphosphate
Ion Channels
Mitochondrial Proteins
Diabetic nephropathy
Mice
03 medical and health sciences
chemistry.chemical_compound
Oxygen Consumption
0302 clinical medicine
Internal medicine
Diabetes mellitus
Internal Medicine
medicine
Animals
Diabetic Nephropathies
Uncoupling Protein 2
030304 developmental biology
Coenzyme Q10
0303 health sciences
Kidney
Vitamins
medicine.disease
Mitochondria
3. Good health
Disease Models
Animal
Oxidative Stress
Proteinuria
medicine.anatomical_structure
Endocrinology
Diabetes Mellitus
Type 2
chemistry
Oxidative stress
Glomerular hyperfiltration
Glomerular Filtration Rate
Zdroj: Diabetologia. 55:1535-1543
ISSN: 1432-0428
0012-186X
DOI: 10.1007/s00125-012-2469-5
Popis: Increased oxygen consumption results in kidney tissue hypoxia, which is proposed to contribute to the development of diabetic nephropathy. Oxidative stress causes increased oxygen consumption in type 1 diabetic kidneys, partly mediated by uncoupling protein-2 (UCP-2)-induced mitochondrial uncoupling. The present study investigates the role of UCP-2 and oxidative stress in mitochondrial oxygen consumption and kidney function in db/db mice as a model of type 2 diabetes.Mitochondrial oxygen consumption, glomerular filtration rate and proteinuria were investigated in db/db mice and corresponding controls with and without coenzyme Q10 (CoQ10) treatment.Untreated db/db mice displayed mitochondrial uncoupling, manifested as glutamate-stimulated oxygen consumption (2.7 ± 0.1 vs 0.2 ± 0.1 pmol O(2) s(-1) [mg protein](-1)), glomerular hyperfiltration (502 ± 26 vs 385 ± 3 μl/min), increased proteinuria (21 ± 2 vs 14 ± 1, μg/24 h), mitochondrial fragmentation (fragmentation score 2.4 ± 0.3 vs 0.7 ± 0.1) and size (1.6 ± 0.1 vs 1 ± 0.0 μm) compared with untreated controls. All alterations were prevented or reduced by CoQ10 treatment. Mitochondrial uncoupling was partly inhibited by the UCP inhibitor GDP (-1.1 ± 0.1 pmol O(2) s(-1) [mg protein](-1)). UCP-2 protein levels were similar in untreated control and db/db mice (67 ± 9 vs 67 ± 4 optical density; OD) but were reduced in CoQ10 treated groups (43 ± 2 and 38 ± 7 OD).db/db mice displayed oxidative stress-mediated activation of UCP-2, which resulted in mitochondrial uncoupling and increased oxygen consumption. CoQ10 prevented altered mitochondrial function and morphology, glomerular hyperfiltration and proteinuria in db/db mice, highlighting the role of mitochondria in the pathogenesis of diabetic nephropathy and the benefits of preventing increased oxidative stress.
Databáze: OpenAIRE
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