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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 #80203
Title: CATALASE-OVEREXPRESSING TRANSGENIC MOUSE HEART IS RESISTANT TO ISCHEMIA- REPERFUSION INJURY

Author
item LI, GUANGQIU - UNIVERSITY OF LOUISVILLE
item CHEN, YAN - UNIVERSITY OF LOUISVILLE
item Saari, Jack
item KANG, JAMES - UNIVERSITY OF LOUISVILLE

Submitted to: American Journal of Physiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/16/1997
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 can be destructive to tissues if not controlled by protective enzymes. 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. Our objective 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. In this study, we used such (transgenic) mice in which heart catalase activity was 60 times normal. Hearts were removed and infused with fluids and oxygen. Force of f contraction of heart was monitored and solution leaving the heart was collected. Heart attacks were simulated by stopping flow to the heart for 50 min and resuming flow for 90 min. Depression of heart-pumping force and tissue damage caused by simulated heart attacks were reduced by the presence of high catalase activity in the heart. This finding 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: Myocardial ischemia-reperfusion injury is at least partially mediated by oxygen-derived free radicals. Catalase is a major enzyme involved in detoxification of hydrogen peroxide. The activity of catalase in the heart is very low, which may be a factor responsible for the high sensitivity of the heart to ischemia-reperfusion injury. The present study was undertaken to determine whether elevation of catalase specifically in the heart of transgenic mice can provide protection against ischemia-reperfusion injury. Hearts were isolated from transgenic mice that overexpressed catalase in the heart about 60-fold higher than normal and form nontransgenic littermates. The hearts were subjected to 50 min of warm (37 deg C) zero-flow ischemia followed by up to 90 min reflow. Compared with nontransgenic controls, transgenic hearts showed significantly improved recovery of contractile force (75% versus 25% and the end of 90 min reperfusion, p<0.01). Efflux of creatine kinase was reduced by about 50% and the zone of myocardial infarction as demarcated by triphenyltetrazolium at the end of reperfusion was reduced by about 40% in transgenic hearts compared with nontransgenic controls. These findings support the view that hydrogen peroxide is an important cause of ischemia- reperfusion damage, and suggest that protection may be provided by elevation of catalase activity.