|Newman Jr, Samuel|
Submitted to: Journal of Federation of American Societies for Experimental Biology
Publication Type: Abstract Only
Publication Acceptance Date: November 10, 2005
Publication Date: March 7, 2006
Citation: Johnson, W.T., Newman, Jr., S.M. 2006. Cardiac mitochondrial function is altered in the adult offspring of copper-deficient dams [abstract]. Journal of Federation of American Societies for Experimental Biology. 20(5):A1065. Technical Abstract: Prolonged reduction in cardiac cytochrome c oxidase (CCO) activity in neonates caused by maternal copper (Cu) deficiency during fetal and postnatal heart development may have pathophysiological consequences in the adult heart. Dams were fed AIN93G diets containing either 1 mg Cu/kg (CuD dams) or 6 mg Cu/kg (CuA dams) beginning 3 weeks before conception and ending 3 weeks after birth. CCO measured in isolated cardiac mitochondria was 51% lower in the 21-day-old pups of CuD dams compared to pups of CuA dams. Cardiac CCO activity in the offspring of CuD dams was 22% lower after 6 weeks of Cu repletion and 14% lower after 9 months of Cu repletion compared to the offspring of CuA dams. Electron micrographs showed that size of the dense deposits and the cellular volume occupied by the deposits in cardiomyocytes were 105% greater and 75% greater, respectively, in the offspring of CuD dams repleted with Cu for 9 months compared to the offspring repleted for 6 weeks. The comparable rise in the size of the dense deposits in the offspring of CuA dams was 40% but their relative volume was unchanged. After 9 months of Cu repletion, the rate of hydrogen peroxide generation by cardiac mitochondria using glutamate/malate as substrate was 24% greater in the offspring of CuD dams compared to the offspring of CuA dams. Increased hydrogen peroxide production by cardiac mitochondria and the increase in the relative volume and size of dense deposits in cardiomyocytes are consistent with increased oxidative stress and damage resulting from the partial reduction of CCO activity in the adult Cu-repleted offspring of CuD dams.