Protection of cardiac mitochondria by overexpression of MnSOD reduces diabetic cardiomyopathy.
We previously reported damage and elevated biogenesis in cardiac mitochondria of a type 1 diabetic mouse model and proposed that mitochondria are one of the major targets of oxidative stress. In this study, we targeted overexpression of the mitochondrial antioxidant protein manganese superoxide dismutase (MnSOD) to the heart to protect cardiac mitochondria from oxidative damage. Transgenic hearts had a 10- to 20-fold increase in superoxide dismutase (SOD) activity, and the transgenic SOD was located in mitochondria. The transgene caused a twofold increase in cardiac catalase activity. MnSOD transgenic mice demonstrated normal cardiac morphology, contractility, and mitochondria, and their cardiomyocytes were protected from exogenous oxidants. Crossing MnSOD transgenic mice with our type 1 model tested the benefit of eliminating mitochondrial reactive oxygen species. Overexpression of MnSOD improved respiration and normalized mass in diabetic mitochondria. MnSOD also protected the morphology of diabetic hearts and completely normalized contractility in diabetic cardiomyocytes. These results showed that elevating MnSOD provided extensive protection to diabetic mitochondria and provided overall protection to the diabetic heart.
Shen
Xia
X
Department of Pathology, University of Washington, Seattle, USA.
Zheng
Shirong
S
Metreveli
Naira S
NS
Epstein
Paul N
PN
D000818:Animals; D009202:Cardiomyopathies / Q000517:prevention & control*; D002374:Catalase / Q000378:metabolism; D048909:Diabetes Complications / Q000517:prevention & control*; D005978:Glutathione / Q000032:analysis; D051379:Mice; D008822:Mice, Transgenic; D008929:Mitochondria, Heart / Q000201:enzymology*; D009200:Myocardial Contraction; D032383:Myocytes, Cardiac / Q000378:metabolism; D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase / Q000235:genetics / Q000502:physiology*
D017382:Reactive Oxygen Species; D002374:Catalase; D013482:Superoxide Dismutase; D005978:Glutathione