Repression of hypoxia-reoxygenation injury in the catalase-overexpressing heart of transgenic mice
1997
Chen, Yan | Yu, Anding | Saari, Jack T. | Kang, Y James
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.
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