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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 #103572
Title: ALTERATIONS IN HYPERTROPHIC GENE EXPRESSION BY DIETARY COPPER RESTRICTION IN MOUSE HEART

Author
item KANG, Y - UNIV. OF LOUISVILLE
item WU, HUIYUN - UNIV. OF LOUISVILLE
item Saari, Jack

Submitted to: American Society for Experimental Biology and Medicine Proceedings
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/8/1999
Publication Date: 3/1/2000
Citation: Kang, Y.J., Wu, H., Saari, J.T. 2000. Alterations in hypertrophic gene expression by dietary copper restriction in mouse heart. Proceedings of the Society for Experimental Biology and Medicine. 223:282-287.

Interpretive Summary: Severe dietary copper deficiency causes heart enlargement in laboratory rodents. The purpose of the present study was to determine whether copper deficiency causes the same changes in genetic expression of proteins that are observed when heart enlargement is caused by other stressors. When heart enlargement is caused by high blood pressure, for instance, the genetic expression of two contractile proteins and a peptide that is responsible for lowering blood pressure are elevated in the ventricle (the large pumping chamber) of the heart. We found that the same changes occurred in hearts enlarged by copper deficiency. This indicates that the molecular processes leading to heart enlargement are independent of the cause of the enlargement. This is important not only because it helps to define the molecular changes that occur in hearts of copper deficient animals, but because it suggests that copper deficiency may be used as an experimental model for studying heart enlargement that may be easier, less stressful and thus preferable to other inducers of heart enlargement. This information will be useful to scientists interested in effects of dietary copper restriction on the cardiovascular system, scientists studying the mechanisms of heart enlargement and members of the general public interested in copper nutrition.

Technical Abstract: Dietary copper (Cu) restriction causes a similar hypertrophic cardiomyopathy as that induced by work overload in rodent models. A possible change in the program of hypertrophic gene expression, however, has not been studied in the Cu-deficient heart. This study was thus undertaken to fill this gap. Dams of mouse pups were placed on a Cu- deficient diet (0.35 mg/kg diet) or a Cu adequate control diet (6.10 mg/kg) on the fourth day after birth, and weanling; mice continued on the same diet until they were sacrificed. After these animals were fed for 5 weeks, Cu concentration were dramatically decreased in the heart and the liver of the mice on Cu-deficient diet. Corresponding to these changes, serum ceruloplasmin concentration and hepatic Cu, Zn-superoxide dismutase activities were significantly (p<0.05) depressed. The size of the Cu- deficient hearts was almost double that of the Cu adequate ones as estimed from the ratio of heart weight to body weight. The abundances of nRNAs for atrial natriuretic factor, beta-myosin heavy chain, and alpha-skeletal action in left ventricles were all significantly increased in the Cu- deficient hearts. Furthermore, Cu deficiency activated the expression of c-myc oncogene in the left ventricle. This study thus demonstrates that a molecular program of re-expression of embryonic genes, similar to that shown in the work overloaded heart, was activated in the hypertrophied heart induced by Cu deficiency.