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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 #98550
Title: SUPPRESSION OF COPPER DEFICIENCY-INDUCED HYPERTROPHY IN METALLOTHIONEIN OVEREXPRESSING TRANSGENIC MOUSE HEARTS

Author
item KANG, Y - UNIVERSITY OF LOUISVILLE
item WU, H - UNIVERSITY OF LOUISVILLE
item Saari, Jack

Submitted to: Experimental Biology
Publication Type: Abstract Only
Publication Acceptance Date: 4/17/1999
Publication Date: N/A
Citation: N/A

Interpretive Summary:

Technical Abstract: Dietary copper restriction causes heart hypertrophy in rodents. Several studies have indicated that this cardiomyopathy is mediated by oxidative stress. Metallothionein (MT), a low molecular weight and cysteine rich protein, has been shown to protect the heart from oxidative injury. It is therefore hypothesized that MT inhibits copper deficiency-induced heart hypertrophy. To test this, a specific cardiac MT overexpressing transgenic mouse model was used. MT concentrations in the transgenic hearts were about 20-fold higher than that in the non-transgenic littermates. Other antioxidant systems were not different between the two substrains. Dams of both transgenic pups and non-transgenic littermates were fed copper deficient diet starting on the fourth day post delivery and the weaned mice were continued on the same diet until they were sacrificed. Heart hypertrophy developed in these animals by the fourth week of the copper deficient diet and aggressively progressed until the en of the experiment (6 wks). MT overexpression did not prevent the occurrence of heart hypertrophy, but inhibited the progression of this cardiomyopathy, which correlated with the suppression by MT of cardiac lipid peroxidation and the inhibition of fetal myocardial gene express. The results suggest that MT indeed suppresses the development of copper deficiency-induced heart hypertrophy, which is at least partially mediated by oxidative stress. Supported in part by a USDA grant 9604531.