Friederich-Persson 2012 Diabetologia: Difference between revisions
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{{Publication | {{Publication | ||
|title=Persson MF, 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 [Epub ahead of print]. Β | |title=Persson MF, 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 [Epub ahead of print]. | ||
|info=[http://www.ncbi.nlm.nih.gov/pubmed?term=Coenzyme%20Q10%20prevents%20GDP-sensitive%20mitochondrial%20uncoupling%2C%20glomerular%20hyperfiltration%20and%20proteinuria%20in%20kidneys%20from%20db%2Fdb%20mice%20as%20a%20model%20of%20type%202%20diabetes%20 PMID: 22311417] | |info=[http://www.ncbi.nlm.nih.gov/pubmed?term=Coenzyme%20Q10%20prevents%20GDP-sensitive%20mitochondrial%20uncoupling%2C%20glomerular%20hyperfiltration%20and%20proteinuria%20in%20kidneys%20from%20db%2Fdb%20mice%20as%20a%20model%20of%20type%202%20diabetes%20 PMID: 22311417] | ||
|authors=Persson MF, FranzΓ©n S, Catrina SB, Dallner G, Hansell P, Brismar K, Palm F | |authors=Persson MF, FranzΓ©n S, Catrina SB, Dallner G, Hansell P, Brismar K, Palm F | ||
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CONCLUSIONS/INTERPRETATION: Β | CONCLUSIONS/INTERPRETATION: Β | ||
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. | 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. | ||
|keywords=db/db mice, Β | |keywords=db/db mice, | ||
|mipnetlab=SE Uppsala Liss P | |||
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{{Labeling | {{Labeling |
Revision as of 14:58, 3 April 2012
Persson MF, 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 [Epub ahead of print]. |
Persson MF, FranzΓ©n 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:
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: z in prep"z in prep" is not in the list (Heart, Skeletal muscle, Nervous system, Liver, Kidney, Lung;gill, Islet cell;pancreas;thymus, Endothelial;epithelial;mesothelial cell, Blood cells, Fat, ...) of allowed values for the "Tissue and cell" property., Kidney Preparation: z in prep"z in prep" is not in the list (Intact organism, Intact organ, Permeabilized cells, Permeabilized tissue, Homogenate, Isolated mitochondria, SMP, Chloroplasts, Enzyme, Oxidase;biochemical oxidation, ...) of allowed values for the "Preparation" property. Enzyme: z in prep"z in prep" is not in the list (Adenine nucleotide translocase, Complex I, Complex II;succinate dehydrogenase, Complex III, Complex IV;cytochrome c oxidase, Complex V;ATP synthase, Inner mt-membrane transporter, Marker enzyme, Supercomplex, TCA cycle and matrix dehydrogenases, ...) of allowed values for the "Enzyme" property. Regulation: z in prep"z in prep" is not in the list (Aerobic glycolysis, ADP, ATP, ATP production, AMP, Calcium, Coupling efficiency;uncoupling, Cyt c, Flux control, Inhibitor, ...) of allowed values for the "Respiration and regulation" property.
HRR: Oxygraph-2k