| Authors |
Li Y, Wende AR, Nunthakungwan O, Huang Y, Hu E, Jin H, Boudina S, Abel ED,
Jalili T
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| Submitted By |
Submitted Externally on 3/4/2015 |
| Status |
Published |
| Journal |
The FEBS journal |
| Year |
2012 |
| Date Published |
2/1/2012 |
| Volume : Pages |
279 : 599 - 611 |
| PubMed Reference |
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| Abstract |
We hypothesized that oxidative stress may contribute to the development of
hypertrophy observed in mice with cardiac specific ablation of the insulin
sensitive glucose transporter 4 gene (GLUT4, G4H(-/-) ). Measurements of
oxidized glutathione (GSSG) in isolated mitochondria and whole heart homogenates
were increased resulting in a lower ratio of reduced glutathione (GSH) to GSSG.
Membrane translocation of the p67(phox) subunit of cardiac NADPH oxidase 2
(NOX2) was markedly increased in G4H(-/-) mice, suggesting elevated activity. To
determine if oxidative stress was contributing to cardiac hypertrophy,
4-week-old control (Con) and G4H(-/-) mice were treated with either tempol (T, 1
mm, drinking water), a whole cell antioxidant, or Mn(III) tetrakis (4-benzoic
acid) porphyrin chloride (MnTBAP, 10 mg路kg(-1) , intraperitoneally), a
mitochondrial targeted antioxidant, for 28 days. Tempol attenuated cardiac
hypertrophy in G4H(-/-) mice (heart : tibia, Con 6.82 卤 0.35, G4H(-/-) 8.83 卤
0.34, Con + T 6.82 卤 0.46, G4H(-/-) + T 7.57 卤 0.3), without changing GSH :
GSSG, glutathione peroxidase 4 or membrane translocation of the p67(phox) .
Tempol did not modify phosphorylation of glycogen synthase kinase 3脽 or
thioredoxin-2. In contrast, MnTBAP lowered mitochondrial GSSG and improved GSH :
GSSG, but did not prevent hypertrophy, indicating that mitochondrial oxidative
stress may not be critical for hypertrophy in this model. The ability of tempol
to attenuate cardiac hypertrophy suggests that a cytosolic source of reactive
oxygen species, probably NOX2, may contribute to the hypertrophic phenotype in
G4H(-/-) mice.
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