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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 #71261
Title: COPPER DEFICIENCY CAUSES IN VIVO OXIDATIVE MODIFICATION OF ERYTHROCYTE MEMBRANE PROTEINS IN RATS

Author
item Johnson, William
item LABERGE, THOMAS - U NORTH DAKOTA
item SUKALSKI, KATHERINE - U NORTH DAKOTA

Submitted to: Trace Elements in Man and Animals International Symposium
Publication Type: Proceedings
Publication Acceptance Date: 5/19/1996
Publication Date: N/A
Citation: N/A

Interpretive Summary: Oxidants, which are chemicals capable of damaging cellular molecules such as lipids, DNA and proteins, are continuously produced as by- products from the metabolism of the oxygen we breath. Accumulation of damage caused by oxidants contributes to the development of a variety of degenerative diseases, including cardiovascular disease, cancer, degenerative brain diseases, and cataracts. Because oxidants are a serious threat to the health of an organism, a variety of mechanisms have evolved to defend against them. An important component of the antioxidant defense system is a copper-containing enzyme called superoxide dismutase (SOD). During dietary copper deficiency, the activity of SOD decreases in several tissues and red blood cells. Thus, it is possible that copper deficiency increases the occurrence of oxidant damage to cellular components. The red blood cell in particular may be a good target for oxidant damage during copper deficiency because its SOD activity is markedly reduced and it constantly produces the oxidant, superoxide. It was found that the membranes of red blood cells obtained from copper-deficient rats contained proteins that were oxidatively modified. Spectrin, a protein that is important for maintaining the structural integrity of the red cell membrane, was specifically damaged by copper deficiency. Because spectrin-like proteins are found in a variety of tissues, their oxidation may be important to the development of pathologies associated with copper deficiency. In a larger sense, these studies suggest that copper is an important nutrient that can help retard the oxidation process and slow the development of degenerative disease.

Technical Abstract: It has been postulated that oxidative damage contributes to the pathology associated with copper (Cu) deficiency because the activity of copper-zinc superoxide dismutase (Cu,ZnSOD) is decreased in several organs. Erythrocytes in particular are probable targets for oxidative damage because they are exposed to high amounts of oxygen and constantly generate superoxide from the autoxidation of heme iron. In the present study, the protein carbonyl and lipid hydroperoxide contents of erythrocyte membranes from rats maintained on control and Cu-deficient diets for 35 days were used as indices of oxidative damage. Prior to membrane isolation, the cells were separated into young and old populations on a Percoll density gradient. Although Cu deficiency reduced erythrocyte Cu,ZnSOD activity in excess of 60%, lipid hydroperoxide content in the membranes was low and unaffected by Cu status but was slightly higher in young cells. Western blot immunoassay for phenylhydrazine derivatives of protein carbonyl groups showed that the carbonyl content of the alpha subunit of spectrin was increased 30% by Cu deficiency. However, the carbonyl content was not affected by cell age. Thus, the erythrocyte cytoskeleton may be particularly sensitive to attack by reactive oxygen species during Cu deficiency.