Repression of hypoxia-reoxygenation injury in the catalase-overexpressing heart of transgenic mice.
Hypoxia-reoxygenation injury results at least in part from reactive oxygen free radicals. Catalase is a major enzyme involved in detoxification of hydrogen peroxide. The activity of catalase per gram of tissue in the heart is very low, being only about 2% that of liver in rodents and humans, which may be responsible for the high sensitivity of the heart to hypoxia-reoxygenation injury. The present study was undertaken to determine whether elevation of catalase specifically in the heart of transgenic mice could provide protection against hypoxia-reoxygenation injury. Transgenic mice with elevated cardiac catalase 60-fold higher than normal were selected, and the effects of catalase elevation on hypoxia-reoxygenation induced functional and morphological changes in isolated atria were determined. Catalase overexpression ameliorated reductions in contractile force and heart rate caused by hypoxia-reoxygenation, and eliminated reoxygenation-induced arrhythmia. The catalase-overexpressing transgenic atria were also highly resistant to hypoxia-reoxygenation-induced morphological alterations, as examined by electron microscopy. Use of cardiac catalase-overexpressing transgenic mice thus demonstrates that hydrogen peroxide is involved in hypoxia-reoxygenation cardiotoxicity, and that this mouse model provides a useful tool for study of free radical mechanism in the heart damage.
Chen
Y
Y
Department of Medicine, University of Louisville School of Medicine, Kentucky 40292, USA.
Yu
A
A
Saari
J T
JT
Kang
Y J
YJ
D000818:Animals; D002374:Catalase / Q000502:physiology*; D005609:Free Radicals; D006861:Hydrogen Peroxide / Q000633:toxicity*; D051379:Mice; D008822:Mice, Transgenic; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D017382:Reactive Oxygen Species / Q000378:metabolism
D005609:Free Radicals; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; D002374:Catalase