|Newman Jr, Samuel|
Submitted to: American Aging Association
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/7/2003
Publication Date: 12/1/2003
Citation: Johnson, W.T., Newman, S.M., Jr. 2003. Copper deficiency: A potential model for determining the role of mitochondria in cardiac aging. Journal of the American Aging Association. 26:29-38.
Interpretive Summary: Cellular molecules such as proteins, lipids, and DNA are in constant danger of being damaged by oxidants that are produced as by-products from the metabolism of the oxygen we breath. Mitochondria are particularly good targets for oxidant damage because they are responsible for metabolizing most of the oxygen taken up by cells. An important component of mitochondrial oxygen metabolism is a copper-containing enzyme called cytochrome c oxidase (CCO). When the activity of this enzyme is lowered, as is the case during copper deficiency, the production of oxidants by mitochondria and the potential for oxidative damage are increased. It was found that mitochondria obtained from livers and hearts of copper deficient rats lowered CCO activity and elevated manganese superoxide dismutase (MnSOD) activity. MnSOD helps protect mitochondria from oxidative damage and its content is dependent on mitochondrial oxidant production. Thus, a higher MnSOD content indicates that oxidant production was elevated by copper deprivation. Lowering food intake increased CCO activity and reduced MnSOD activity in heart and liver mitochondria of CuD rats. This finding indicates that increased mitochondrial oxidant production during copper deficiency can be reversed, at least partially, by reducing food intake. However, reducing food intake did not completely protect mitochondrial proteins from oxidative damage during copper deficiency. The accumulation of oxidative damage to mitochondria can contribute to degenerative heart and brain diseases and even minor deficits in mitochondrial function can cause weakness and impair cognitive function. Therefore, the present study suggests that copper is an important nutrient for slowing the development of degenerative diseases.
Technical Abstract: This study evaluated the effects of food restriction on oxidative stress produced in liver and heart mitochondria by copper deficiency. Male, weanling, rats were fed copper-deficient (CuD) (0.3 mg Cu/g) and copper- adequate (CuA) (5.0 mg Cu/g) diets either ad libitum or at 80% of the ad libitum intake. After 5 weeks of dietary treatment, cytochrome c oxidase (CCO) activity was decreased in liver and heart mitochondria and manganese superoxide dismutase (MnSOD) was increased in heart mitochondria obtained from CuD rats. However, compared to feeding ad libitum, restricting food intake of copper-deficient rats increased CCO activity (P<0.05) in liver mitochondria (80%) and in heart mitochondria (60%) and decreased (P<0.05) MnSOD activity in liver mitochondria (40%) and in heart mitochondria (26%). These findings indicate that copper-deficiency produced a pro- oxidant cellular environment that induced MnSOD activity. The findings also indicate that food restriction may ameliorate mitochondrial oxidative stress by maintaining higher levels of CCO activity in liver and heart mitochondria. However, food restriction had no effect on the carbonyl content of mitochondrial proteins in livers and hearts from CuD rats. Thus, the amelioration of oxidative stress by a 20% reduction in food intake was not sufficient to prevent oxidative damage to mitochondrial proteins. Glutathione peroxidase activity (GPX) in heart, but not liver, mitochondria was elevated (P<0.05) in CuD rats. Food restriction also prevented mitochondrial hypertrophy in hearts, but not in livers, of CuD rats. These findings suggest that heart and liver may have different mechanisms for adapting to oxidative stress during copper deficiency.