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SOD2 overexpression: enhanced mitochondrial tolerance but absence of effect on UCP activity.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Silva, Jose Denison Prado Shabalina, Irina G. Dufour, Eric Petrovic, Natasa B. Backlund, Emma C. Hultenby, Kjell R. Wibom, Rolf Nedergaard, Jan Cannon, Barbara A. Larsson, Nils-Göran |
| Copyright Year | 2005 |
| Abstract | We have created P1 artificial chromosome transgenic mice expressing the human mitochondrial superoxide dismutase 2 (SOD2) and thus generated mice with a physiologically controlled augmentation of SOD2 expression leading to increased SOD2 enzyme activities and lowered superoxide levels. In the transgenic mice, effects on mitochondrial function such as enhanced oxidative capacity and greater resistance against inducers of mitochondrial permeability were observed. Superoxide in the mitochondrial matrix has been proposed to activate uncoupling proteins (UCPs), thus providing a feedback mechanism that will lower respiratory chain superoxide production by increasing a proton leak across the inner mitochondrial membrane. However, UCP1 and UCP3 activities and mitochondrial ATP production rates were not altered in isolated mitochondria from SOD2 transgenic mice, despite lowered superoxide levels. Globally, the transgenic mice displayed normal resting metabolic rates, indicating an absence of effect on any UCP activities, and normal oxygen consumption responses after norepinephrine injection. These results strongly suggest that endogenously generated matrix superoxide does not regulate UCP activity and in vivo energy expenditure. |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://emboj.embopress.org/content/embojnl/24/23/4061.full.pdf |
| PubMed reference number | 16281056v1 |
| Volume Number | 24 |
| Issue Number | 23 |
| Journal | The EMBO journal |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Activation action Adenosine Triphosphate Chromosomes, Artificial Energy Metabolism Inner mitochondrial membrane Lowered (qualifier value) Mitochondrial Diseases Mitochondrial Inheritance Mitochondrial Membranes Mitochondrial Uncoupling Proteins Norepinephrine Oxygen Consumption Protons Rest SOD2 gene SOD2 protein, human Superoxide Dismutase Superoxides UCP1 gene UCP1 wt Allele |
| Content Type | Text |
| Resource Type | Article |
