| First Author | Li Y | Year | 2012 |
| Journal | FEBS J | Volume | 279 |
| Issue | 4 | Pages | 599-611 |
| PubMed ID | 22221582 | Mgi Jnum | J:194137 |
| Mgi Id | MGI:5470381 | Doi | 10.1111/j.1742-4658.2011.08450.x |
| Citation | Li Y, et al. (2012) Cytosolic, but not mitochondrial, oxidative stress is a likely contributor to cardiac hypertrophy resulting from cardiac specific GLUT4 deletion in mice. FEBS J 279(4):599-611 |
| abstractText | 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.kg(-1) , intraperitoneally), a mitochondrial targeted antioxidant, for 28 days. Tempol attenuated cardiac hypertrophy in G4H(-/-) mice (heart : tibia, Con 6.82 +/- 0.35, G4H(-/-) 8.83 +/- 0.34, Con + T 6.82 +/- 0.46, G4H(-/-) + T 7.57 +/- 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 3beta 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. |
