Difference between revisions of "Friederich-Persson 2012 Diabetologia"
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{{Publication | {{Publication | ||
|title=Friederich-Persson M, Franzén 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 55:1535-43. | |title=Friederich-Persson M, Franzén 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 55:1535-43. | ||
|info=[http://www.ncbi.nlm.nih.gov/pubmed | |info=[http://www.ncbi.nlm.nih.gov/pubmed/22311417 PMID: 22311417] | ||
|authors=Friederich-Persson M, Franzen S, Catrina SB, Dallner G, Hansell P, Brismar K, Palm F | |authors=Friederich-Persson M, Franzen S, Catrina SB, Dallner G, Hansell P, Brismar K, Palm F | ||
|year=2012 | |year=2012 | ||
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CONCLUSIONS/INTERPRETATION: | 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. | 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 | |keywords=db/db mice, Kidney, Mitochondria, Type2 diabetes, Uncoupling protein-2 | ||
|mipnetlab=SE Uppsala Liss P | |mipnetlab=SE Uppsala Liss P | ||
}} | }} | ||
| Line 23: | Line 23: | ||
|organism=Mouse | |organism=Mouse | ||
|tissues=Kidney | |tissues=Kidney | ||
|preparations=Isolated mitochondria | |||
|injuries=Ischemia-reperfusion, Oxidative stress;RONS | |injuries=Ischemia-reperfusion, Oxidative stress;RONS | ||
|diseases=Diabetes | |diseases=Diabetes | ||
|couplingstates=LEAK, OXPHOS | |||
|substratestates=CI, ROX | |||
|instruments=Oxygraph-2k | |instruments=Oxygraph-2k | ||
}} | }} | ||
Revision as of 13:52, 23 September 2016
| Friederich-Persson M, Franzén 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 55:1535-43. |
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 (2.7 ± 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).
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. • Keywords: db/db mice, Kidney, Mitochondria, Type2 diabetes, Uncoupling protein-2
• O2k-Network Lab: SE Uppsala Liss P
Labels: MiParea: Respiration, Genetic knockout;overexpression
Pathology: Diabetes
Stress:Ischemia-reperfusion, Oxidative stress;RONS
Organism: Mouse
Tissue;cell: Kidney
Preparation: Isolated mitochondria
Coupling state: LEAK, OXPHOS
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?
