Author
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Johnson, William |
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Newman Jr, Samuel |
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Submitted to: Journal of Nutritional Biochemistry
Publication Type: Peer Reviewed Journal Publication Acceptance Date: 3/8/2006 Publication Date: 9/1/2006 Citation: Johnson, W.T., Newman Jr, S.M. 2007. Hearts in adult offspring of copper-deficient dams exhibit decreased cytochrome c oxidase activity, increased mitochondrial hydrogen peroxide generation and enhanced formation of intracellular residual bodies. Journal of Nutritional Biochemistry. 18:97-104. Interpretive Summary: Although it is known that copper deficiency during pregnancy produces long-term neurological defects in the first generation, little is known about the long-term effects of maternal copper deficiency on the cardiovascular system in the first generation. This study shows that copper deficiency in rat dams during pregnancy and lactation causes a reduction in cytochrome c oxidase, a copper-dependent enzyme, in heart mitochondria of 21-day-old offspring. Furthermore, cytochrome c oxidase activity can not be fully restored in heart mitochondria of these offspring by either 6 weeks or 9 months of dietary copper supplementation. After 9 months of copper-supplementation, the reduction in cytochrome c oxidase activity in the offspring of copper-deficient dams is associated with an increase in the production of hydrogen peroxide by cardiac mitochondria. Electron microscopic examination of heart tissue from the offspring after 9 months of copper supplementation revealed the presence of a high number of intracellular dense deposits associated with oxidized mitochondrial proteins and lipids. These results indicate that maternal copper deficiency in rats has long-term effects on heart mitochondrial function that increases the level of oxidative damage in first generation adults even when copper status was restored immediately after weaning. It has been estimated from dietary surveys that the dietary intake of copper for 14-16 year-old women and 25-30 year-old women are 0.76 mg/day and 0.94 mg/day, respectively. These copper intakes are below the recommended dietary allowance (RDA) of 1 mg/day for pregnant women and the RDA of 1.3 mg/day for lactating women in these age groups, indicating that a portion of young, pregnant or lactating women are copper deficient. Findings from the present study suggest that these copper-deficient young women may be increasing their childrens’ risk for developing heart disease at some point during their life times. Technical Abstract: The long-term effects of low dietary copper (Cu) intake during pregnancy and lactation on cardiac mitochondria in first generation adult rats was examined. Rat dams were fed diets containing either low (1 mg Cu/kg) or adequate (6 mg Cu/kg levels of dietary Cu beginning 3 weeks before conception and ending 3 weeks after birth. Cytochrome c oxidase (CCO) activity was 51% lower in isolated cardiac mitochondria from the 21-day old offspring of Cu-deficient dams compared to the offspring of Cu-adequate dams. CCO activities in cardiac mitochondria from 63-day-old and 290-day-old offspring were 22% lower and 14% lower, respectively, in the offspring of Cu-deficient dams after they had been repleted with adequate dietary Cu from the time they were 21-days-old. Electron micrographs showed that the size of residual bodies and the cellular volume they occupied in cardiomyocytes rose significantly between 63-days and 290-days in the Cu-repleted offspring of Cu-deficient dams but not in the offspring of Cu-adequate dams. The rate of hydrogen peroxide generation by cardiac mitochondria also was 24% higher in the 290-day-old, repleted offspring of Cu-deficient dams compared to the offspring of Cu-adequate 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 prolonged reduction of CCO activity in the offspsring of the Cu-deficient dams. |
