| First Author | Cong W | Year | 2015 |
| Journal | J Mol Cell Cardiol | Volume | 89 |
| Issue | Pt B | Pages | 314-25 |
| PubMed ID | 26456065 | Mgi Jnum | J:251021 |
| Mgi Id | MGI:6102289 | Doi | 10.1016/j.yjmcc.2015.10.010 |
| Citation | Cong W, et al. (2015) Cardiac-specific overexpression of catalase prevents diabetes-induced pathological changes by inhibiting NF-kappaB signaling activation in the heart. J Mol Cell Cardiol 89(Pt B):314-25 |
| abstractText | Catalase is an antioxidant enzyme that specifically catabolizes hydrogen peroxide (H2O2). Overexpression of catalase via a heart-specific promoter (CAT-TG) was reported to reduce diabetes-induced accumulation of reactive oxygen species (ROS) and further prevent diabetes-induced pathological abnormalities, including cardiac structural derangement and left ventricular abnormity in mice. However, the mechanism by which catalase overexpression protects heart function remains unclear. This study found that activation of a ROS-dependent NF-kappaB signaling pathway was downregulated in hearts of diabetic mice overexpressing catalase. In addition, catalase overexpression inhibited the significant increase in nitration levels of key enzymes involved in energy metabolism, including alpha-oxoglutarate dehydrogenase E1 component (alpha-KGD) and ATP synthase alpha and beta subunits (ATP-alpha and ATP-beta). To assess the effects of the NF-kappaB pathway activation on heart function, Bay11-7082, an inhibitor of the NF-kappaB signaling pathway, was injected into diabetic mice, protecting mice against the development of cardiac damage and increased nitrative modifications of key enzymes involved in energy metabolism. In conclusion, these findings demonstrated that catalase protects mouse hearts against diabetic cardiomyopathy, partially by suppressing NF-kappaB-dependent inflammatory responses and associated protein nitration. |
