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ARS Home » Plains Area » Grand Forks, North Dakota » Grand Forks Human Nutrition Research Center » Dietary Prevention of Obesity-related Disease Research » Research » Publications at this Location » Publication #79273
Title: REPRESSION OF HYPOXIA-REOXYGENATION INJURY IN THE CATALASE OVEREXPRESSING HEART OF TRANSGENIC MICE

Author
item CHEN, YAN - UNIV OF LOUISVILLE
item YU, ANDING - UNIV OF LOUISVILLE
item Saari, Jack
item KANG, JAMES - UNIV OF LOUISVILLE

Submitted to: American Society for Experimental Biology and Medicine Proceedings
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/6/1997
Publication Date: N/A
Citation: N/A

Interpretive Summary: Catalase is a major enzyme involved in detoxification of hydrogen peroxide, a form of highly reactive oxygen that is normally produced by the body but is destructive to tissues. The amount of catalase in the heart is very low, being only about 2% of that of the liver in the mouse. This relative inability to dispose of reactive oxygen species may be responsible for the unusual sensitivity of the heart to oxidative injury. The objective of this research was to determine whether selective elevation of catalase activity in the mouse heart by genetic methods could provide protection against the oxidative stress of a simulated heart attack. The gene for elevated catalase in the heart was successfully inserted and bred into mice. Transgenic mice were used in which the heart catalase activity was 60 times normal. Heart attacks were simulated in isolated heart atria (the heart's small upper chambers) by bubbling nitrogen through their bathing solution followed by re-bubbling with oxygen. Microscopic structural damage and depression of contractile force and heart rate caused by simulated heart attacks were inhibited by the presence of high catalase activity in the heart. This indicates that hydrogen peroxide may play an important role in heart attacks. Such studies will help scientists and consumers to further understand and thus devise preventive measures against damage caused by this important disease process.

Technical Abstract: 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 g tissue in the heart is very low, being only about 2% that of liver in rodents and humans, which many be responsible for the high sensitivity of the heart to hypoxia- reoxygenation. 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 over expression ameliorated reductions in heart rate and force caused by hypoxia-reoxygenation, and eliminated reoxygenation-induced arrhythmia. The catalase over expressing transgenic atria were also highly resistant to hypoxia-reoxygenation induced morphological alterations as examined by electron microscopy. Use of cardiac catalase over expressing transgenic mice thus demonstrates that hydrogen peroxide is involved in hypoxia-reoxygenation cardiotoxicity and this mouse model provides a useful tool for study of free radical injury in the heart.