Mitochondrial oxidative stress and protein kinase care not the regulators of cardiac hypertrophy in mice and cardiac specific glucose transporter 4 deletion

Previous studies have found oxidative stress and PKC activation with the presence of cardiac hypertrophy in diabetic animal models and diabetic patients. Mice with cardiac specific deletion of insulin sensitive glucose transporters (G4H"A) have cardiac hypertrophy, oxidative stress, and PKC activation. The current study hypothesized that oxidative stress might be a driving force of PKC activation, and subsequent cardiac hypertrophy. 4-week-old male and female G4H"A (N= 33), and control mice (N= 37) were treated with 10 mg/kg (IP) of MnTBAP (mitochondrial manganese-dependent SOD mimetic) or vehicle control (5 mM NaOH) every other day for 4 weeks. PKCpiI was the only isoform that was activated in G4H"A as evidenced by increased pPKCot/pII translocation compared to controls. Translocation/activation of pPKCa/pII was reduced to control levels after MnTBAP treatment. G4H"A mice treated with MnTBAP also had lower pPKCS and pPKCs translocation compared to G4H"A treated with vehicle alone. However, the lower PKC translocation did not result in decreased cardiac hypertrophy. Since there was no increase in PKC activation in G4H"/" except for PKCpiI, and subsequent lower PKC5 and s translocation after MnTBAP treatment did not result in prevention of cardiac hypertrophy, this leads to the conclusion that PKC is not a regulator of the hypertrophy in mice with cardiac specific insulin resistance. In addition, mitochondrial oxidative stress may not be an important source of oxidative stress in G4H7" as pharmacologically enhancing mitochondrial antioxidant capacity with MnTBAP was not enough to reduce the hypertrophy.