Alterations in hypertrophic gene expression by dietary copper restriction in mouse heart.
Dietary copper (Cu) restriction causes a hypertrophic cardiomyopathy similar to that induced by work overload in rodent models. However, a possible change in the program of hypertrophic gene expression has not been studied in the Cu-deficient heart. This study was undertaken to fill that gap. Dams of mouse pups were fed 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 dams' diet until they were sacrificed. After 5 weeks of feeding, Cu concentrations were dramatically decreased in the heart and the liver of the mice fed the Cu-deficient diet. Corresponding to these changes, serum ceruloplasmin concentrations and hepatic Cu,Zn-superoxide dismutase activities were significantly (P<0.05) depressed. The size of the Cu-deficient hearts was greatly enlarged as estimated from the absolute heart weight and the ratio of heart weight to body weight. The abundances of mRNAs for atrial natriuretic factor, beta-myosin heavy chain, and alpha-skeletal actin in left ventricles were all significantly increased in the Cu- deficient hearts. Furthermore, Cu deficiency activated the expression of the c-myc oncogene in the left ventricle. This study thus demonstrated that a molecular program of alterations in embryonic genes, similar to that shown in the work-overloaded heart, was activated in the hypertrophied heart induced by Cu deficiency.
Kang
Y J
YJ
Department of Medicine, University of Louisville, Kentucky 40292, USA. yjkang01@athena.louisville.edu
Wu
H
H
Saari
J T
JT
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000235:genetics*; D006332:Cardiomegaly / Q000209:etiology / Q000235:genetics*; D002570:Ceruloplasmin / Q000378:metabolism; D003300:Copper / Q000008:administration & dosage* / Q000378:metabolism; D004032:Diet / Q000009:adverse effects; D004195:Disease Models, Animal; D015870:Gene Expression; D008099:Liver / Q000201:enzymology / Q000378:metabolism; D051379:Mice; D009206:Myocardium / Q000378:metabolism; D018995:Myosin Heavy Chains / Q000235:genetics*; D024501:Nonmuscle Myosin Type IIB; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D013482:Superoxide Dismutase / Q000378:metabolism
D016271:Proto-Oncogene Proteins c-myc; D003300:Copper; D009320:Atrial Natriuretic Factor; D013482:Superoxide Dismutase; D002570:Ceruloplasmin; D024501:Nonmuscle Myosin Type IIB; C103815:nonmuscle myosin type IIB heavy chain; D018995:Myosin Heavy Chains