Friederich-Persson 2012 Diabetologia: Difference between revisions
No edit summary |
|
(No difference)
|
Revision as of 16:00, 8 July 2013
Friederich-Persson M, FranzΓ©n S, Catrina SB, Dallner G, Hansell P, Brismar K, Palm F (2012) Coenzyme Q10 prevents GDP-sensitive mitochondrial uncoupling, glomerular hyperfiltration and proteinuria in kidneys from db/db mice as a model of type 2 diabetes. Diabetologia 55: 1535-1543. |
Friederich-Persson M, Franzen S, Catrina SB, Dallner G, Hansell P, Brismar K, Palm F (2012) Diabetologia
Abstract: AIMS/HYPOTHESIS: 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.
METHODS: Mitochondrial oxygen consumption, glomerular filtration rate and proteinuria were investigated in db/db mice and corresponding controls with and without coenzyme Q10 (CoQ10) treatment.
RESULTS: Untreated db/db mice displayed mitochondrial uncoupling, manifested as glutamate-stimulated oxygen consumption (2.7βΒ±β0.1 vs 0.2βΒ±β0.1 pmol O(2) s(-1) [mg protein](-1)), glomerular hyperfiltration (502βΒ±β26 vs 385βΒ±β3 ΞΌl/min), increased proteinuria (21βΒ±β2 vs 14βΒ±β1, ΞΌg/24 h), mitochondrial fragmentation (fragmentation score 2.4βΒ±β0.3 vs 0.7βΒ±β0.1) and size (1.6βΒ±β0.1 vs 1βΒ±β0.0 ΞΌm) compared with untreated controls. All alterations were prevented or reduced by CoQ10 treatment. Mitochondrial uncoupling was partly inhibited by the UCP inhibitor GDP (-1.1βΒ±β0.1 pmol O(2) s(-1) [mg protein](-1)). UCP-2 protein levels were similar in untreated control and db/db mice (67βΒ±β9 vs 67βΒ±β4 optical density; OD) but were reduced in CoQ10 treated groups (43βΒ±β2 and 38βΒ±β7 OD).
CONCLUSIONS/INTERPRETATION: 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. β’ Keywords: db/db mice
β’ O2k-Network Lab: SE Uppsala Liss P
Labels:
Pathology: Diabetes
Stress:RONS; Oxidative Stress"RONS; Oxidative Stress" is not in the list (Cell death, Cryopreservation, Ischemia-reperfusion, Permeability transition, Oxidative stress;RONS, Temperature, Hypoxia, Mitochondrial disease) of allowed values for the "Stress" property., Genetic Defect; Knockdown; Overexpression"Genetic Defect; Knockdown; Overexpression" is not in the list (Cell death, Cryopreservation, Ischemia-reperfusion, Permeability transition, Oxidative stress;RONS, Temperature, Hypoxia, Mitochondrial disease) of allowed values for the "Stress" property.
Organism: Mouse
Tissue;cell: Kidney
HRR: Oxygraph-2k
Mitochondrial respiration medium for kidney
The intracellular milieu of kidney has a low [K+]. Kidney mitochondria are inhibited by the high [K+] of MiR06.
>> MiPMap - Is this a general issue for the organ, or is it in addition also a species issue?