Sökning: WFRF:(Franzén Stephanie)
> (2012-2014) >
Coenzyme Q10 preven...
Coenzyme Q10 prevents GDP-sensitive mitochondrial uncoupling, glomerular hyperfiltration and proteinuria in kidneys from db/db mice as a model of type 2 diabetes
-
- Friederich Persson, Malou (författare)
- Uppsala universitet,Integrativ Fysiologi,Biomed Centre, Uppsala
-
- Franzén, Stephanie (författare)
- Biomed Centre, Uppsala
-
- Catrina, S-B (författare)
- Karolinska Institutet
-
visa fler...
-
- Dallner, G. (författare)
- Karolinska Institute, Stockholm,Karolinska Institutet, Institutionen för molekylär medicin och kirurgi
-
- Hansell, Peter (författare)
- Uppsala universitet,Integrativ Fysiologi,Biomed Centre, Uppsala
-
- Brismar, K. (författare)
- Karolinska Institutet
-
- Palm, Fredrik (författare)
- Uppsala universitet,Linköpings universitet,Avdelningen för läkemedelsforskning,Hälsouniversitetet,Integrativ Fysiologi
-
visa färre...
-
(creator_code:org_t)
- 2012-02-05
- 2012
- Engelska.
-
Ingår i: Diabetologia. - : Springer Verlag (Germany). - 0012-186X .- 1432-0428. ; 55:5, s. 1535-1543
- Relaterad länk:
-
https://link.springe...
-
visa fler...
-
https://urn.kb.se/re...
-
https://doi.org/10.1...
-
https://urn.kb.se/re...
-
http://kipublication...
-
visa färre...
Abstract
Ämnesord
Stäng
- 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 O2 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 O2 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Fysiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Physiology (hsv//eng)
Nyckelord
- db/db mice
- Kidney
- Mitochondria
- Type 2 diabetes
- Uncoupling protein-2
- MEDICINE
- MEDICIN
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
Hitta via bibliotek
Till lärosätets databas