Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: 11/19/1998
Publication Date: N/A
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 cardia MT overexpressing transgenic mouse model was used. 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 on the copper deficient diet and aggressively progressed until the end of the experiment (6 wks). MT overexpression did not prevent the occurrence of heart hypertrophy, but inhibited the progress of this cardiomyopathy, which correlated with the suppression by MT of the progression of cardiac lipid peroxidation. 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. 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 9504531.