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Mitochondrial oxidative stress does not contribute to cardiac hypertrophy in mice with cardiac specific GLUT4 deletion
Author(s) -
Jalili Thunder,
Nunthakungwan Orathai,
Li Yan,
Jin Huifeng,
Hu Eric,
Wende Adam R,
Abel E. Dale
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.614.21
Subject(s) - medicine , oxidative stress , endocrinology , glutathione , glutathione reductase , muscle hypertrophy , glut4 , chemistry , mitochondrion , insulin resistance , superoxide dismutase , biochemistry , insulin , enzyme , glutathione peroxidase
Cardiac specific ablation of insulin sensitive glucose transporters (GLUT4) in mice (G4H −/− ) results in cardiac hypertrophy via unknown mechanism(s) we hypothesize are related to oxidative stress, as hearts of G4H −/− mice have greater oxidized (GSSG) glutathione and an attenuated ratio of reduced (GSH) glutathione to GSSG vs. controls. To determine the contribution of mitochondrial oxidative stress to cardiac hypertrophy, male and female control (Con) and G4H −/− mice were treated with a mitochondrial targeted superoxide 2 mimetic, MnTBAP [(Mn(III)tetrakis(4‐Benzoic acid) porphyrin Chloride, 10 mg/kg, i.p.] or saline. Male Con and G4H −/− mice had similar levels of mitochondrial GSSG and GSH:GSSG (n=5–6). MnTBAP altered these levels only in Con mice (GSH:GSSG, Con 41±8, G4H −/− 30±4, Con+MnTBAP 56±3, G4H −/− +MnTBAP 37±2). Cardiac hypertrophy (n=6–7) was unchanged after MnTBAP (heart:tibia length, Con 7.2±0.2, G4H −/− 8.9±0.5, Con+MnTBAP 7.9±0.3, G4H −/− +MnTBAP 8.6±0.5). In female G4H −/− mice even though GSSG (n=5–11) was reduced by MnTBAP (Con 19±2, G4H −/− 47±6, Con+MnTBAP 18±2 vs. G4H −/− +MnTBAP 30±4), there was no reduction in cardiac hypertrophy (n=7–10, Con 6.3±0.2, G4H −/− 7.9±0.3, Con+MnTBAP 6.2±0.1, G4H −/− +MnTBAP 7.7±0.3). We conclude that mitochondrial oxidative stress does not contribute to cardiac hypertrophy in this model of cardiac specific insulin resistance. Supported by NIH HL085226.