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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 #67219
Title: TRANSGENIC MICE OVEREXPRESSING CATALASE SPECIFICALLY IN THE HEART FOR STUDYING COPPER DEFICIENCY INDUCED CARDIAC OXIDATIVE INJURY

Author
item KANG, Y - U NORTH DAKOTA
item CHEN, YAN - U NORTH DAKOTA
item Saari, Jack

Submitted to: Trace Elements in Man and Animals International Symposium
Publication Type: Abstract Only
Publication Acceptance Date: 5/19/1996
Publication Date: N/A
Citation: N/A

Interpretive Summary:

Technical Abstract: Our previous studies have shown that copper deficiency selectively induces lipid peroxidation in the heart of rats. Further study revealed that the heart contains weak antioxidant systems relative to other tissues. In particular, catalase activity per g heart tissue is very low, being only about 2% that of the liver. Because catalase is a major enzyme involved in detoxification of hydrogen peroxide, (H2O2) in mammalian cells, this relative deficit ability of the heart to dispose of reactive oxygen species may be responsible for the high sensitivity of the heart to oxidative injury. The objective of this research is to determine whether elevation of catalase activity specifically in the heart of transgenic mice can provide protection against oxidative cardiotoxicity. A transgene for overexpression of catalase in the heart was constructed to contain fragments from the rat catalase cDNA ligated behind the alpha cardiac myosin heavy chain promotor. The transgenic mice were identified using Southern and Dot blot, and PCR procedure. Catalase activities and its mRNA levels in the heart and other organs were measured. The results show that 15 transgenic mouse lines were produced. Only catalase, not other anti- oxidants including superoxide dismutase, GSH peroxidase, GSH reductase, GSH, and metallothionein, is overexpressed in the heart, in other atria and ventricles. Each transgenic line exhibits a stably elevated catalase activity, ranging from 2- to 500-fold higher than normal. This enzyme activity is not altered in any other organs including liver, kidneys, lungs, and skeletal muscles. This model is ideal to study the role of catalase in protection against copper deficiency induced oxidative injury to the heart. Supported by NIH Grant CA68125 and USDA Grant 9500668.