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Science Index

Copper Trace Mineral

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Title
Aspects of cardiomyopathy are exacerbated by elevated dietary fat in copper-restricted rats.
Author
Jalili T; Medeiros DM; Wildman RE
Address
Department of Human Nutrition and Food Management' Ohio State University' Columbus 43210' USA.
Source
J Nutr, 126(4):807-16 1996 Apr
Abstract
The obJective of this study was to determine if a high fat diet having a 2:1 saturated-polyunsaturated fatty acid ratio exacerbates signs of copper deficiency. Male weanling Long-Evans rats were randomly placed into one of the following treatment groups: adequate copper low fat or deficient copper high fat. The levels of fat used were 31 or 12% of daily energy' and copper concentrations were 94.5 micromol/kg and <15.8 micromol/kg in the copper-adequate and copper-deficient diets' respectively. Cardiac hypertrophy as well as lower liver copper levels and superoxide dismutase activity were observed in both groups of copper-deficient rats. Irrespective of copper level' consumption of the high fat diet resulted in the thickening of the interventricular septum and left ventricular free wall. Electrocardiograms revealed that the copper-deficient high fat diet led to a significantly smaller QT interval compared with all other groups. Significantly greater S-wave voltage due to copper deficiency was observed. Significantly lower heart cytochrome c oxidase (CCO) activity was found in the copper-deficient groups with the copper deficient high fat group showing the lowest activity. Western blots of the cardiac non-myofibrillar fraction demonstrated lower amounts of CCO nuclear encoded peptides in the copper-deficient groups' with the least amount seen in the copper-deficient high fat treatment. These data suggest that a high level of dietary fat exacerbates some of the signs of copper deficiency.

Title
Antioxidant defense system in lung of male and female rats: interactions with alcohol' copper' and type of dietary carbohydrate.
Author
Fields M; Lewis CG; Lure MD
Address
Beltsville Human Nutrition Research Center' US Department of Agriculture' Agricultural Research Service' MD 20705' USA.
Source
Metabolism, 45(1):49-56 1996 Jan
Abstract
Male and female rats were used to investigate the effects of type of dietary carbohydrate (CHO)' copper' and ethanol consumption on lung antioxidant enzyme activities and levels of phosphorylated compounds in whole blood. copper-deficient female rats exhibited a greater degree of copper deficiency than males' as assessed by hepatic copper concentration and hepatic copper superoxide dismutase (CuSOD) activity. However' copper-deficient male rats fed fructose-containing diets exhibited greater growth retardation' anemia' and heart hypertrophy than females consuming the same diets and males fed starch. In addition' one of 10 copper-deficient male rats that ate a fructose-based diet and drank water and one of 10 copper-deficient male rats that ate a starch-based diet and drank ethanol died. copper-deficient' starch-fed males exhibited the highest activities of glutathione peroxidase (GSH-Px) and catalase as compared with fructose-fed rats. Ethanol consumption elevated the activities of GSH-Px and catalase. copper-deficient female rats exhibited higher catalase but lower GSH-Px activities than males. It is suggested that in copper deficiency' the ability to increase antioxidant enzyme activities in rats consuming starch is greater than in rats consuming fructose. Rats fed starch are provided with a greater degree of protection against oxidative damage than rats fed fructose. In addition' polyphosphorylated compounds in blood were reduced in copper-deficient male rats that consumed fructose-based diets. This may impair supply of oxygen to tissues.

Title
Defects of copper deficiency in rats are modified by dietary treatments that affect glycation.
Author
Saari JT; Bode AM; Dahlen GM
Address
U.S. Department of Agriculture' Agricultural Research Service' Grand Forks Human Nutrition Research Center' ND' USA.
Source
J Nutr, 125(12):2925-34 1995 Dec
Abstract
We examined the hypothesis that nonenzymatic glycosylatin of proteins (glycation) contributes to the defects of copper deficiency. We studied copper-adequate and -deficient rats while altering two factors known to affect glycation: type of dietary carbohydrate and amount of food intake. copper deficiency caused cardiac enlargement and anemia' decreased erythrocyte osmotic fragility' enhanced heart lipid peroxidation' increased the percentage of glycated hemoglobin (Hb A1) and reduced staining of lens crystallins on SDS-PAGE gels (suggestive of glycation). Increasing dietary sucrose reduced organ copper concentration' exacerbated the rise in Hb A1 and worsened the anemia caused by copper deficiency. Food restriction ameliorated heart and erythrocyte defects' reduced the percentage of glycated hemoglobin and heart peroxidation and also improved heart and liver copper status in copper-deficient rats. These findings indicate that copper deficiency enhances glycation and that sucrose may exacerbate some defects of copper deficiency by enhancing glycation. Inhibition of defects of copper deficiency by food restriction suggests that glycation and/or peroxidation may contribute to those defects.

Title
Antioxidant enzyme gene transcription in copper-deficient rat liver.
Author
Lai CC; Huang WH; Klevay LM; Gunning WT 3rd; Chiu TH
Address
Department of Pharmacology' Medical College of Ohio' Toledo 43699-0008' USA.
Source
Free Radic Biol Med, 21(2):233-40 1996
Abstract
Antioxidant enzymes' Cu/Zn- and Mn-superoxide dismutase' catalase' and glutathione peroxidase' constitute an important defense mechanism against cytotoxicity of reactive oxygen species. copper is essential for the activity of Cu/Zn-superoxide dismutase. Oxidative stress' therefore' is expected in organs of rats fed copper-deficient diet due to reduced Cu/Zn-superoxide dismutase activity. Our previous studies have shown that the expression of antioxidant enzymes was altered in copper-deficient rat liver. The present report was undertaken to study further the transcription of these enzymes in liver nuclei of rats made copper-deficient for 4 weeks. While copper deficiency decreased the copper in liver by about 80%' it did not alter the copper content in liver nuclei. In spite of a 100% elevation in nuclear iron concentration' liver nuclei from copper-deficient rats showed normal appearance. The transcriptional rates for Cu/Zn-superoxide dismutase' glutathione peroxidase' and glyceraldehyde-3-phosphate dehydrogenase were not altered by dietary copper deprivation. In contrast' transcriptional rates for Mn-superoxide dismutase and beta-actin were increased but that for catalase was reduced in the nuclei isolated from the copper-deficient rat liver. These results suggest that oxidative stress' resulting from copper deficiency' differentially modulates the gene transcription for the antioxidant enzymes in rat liver.

Title
Concentrations of thyroid hormones in serum and activity of hepatic 5` monodeiodinase in copper-deficient rats.
Author
Kralik A; Kirchgessner M; Eder K
Address
Institut f ur Ern ahrungsphysiologie' Technische Universit at M unchen' Freising-Weihenstephan.
Source
Z Ernahrungswiss, 35(3):288-91 1996 Sep
Abstract
The aim of the present study was to investigate the effect of copper deficiency on thyroid hormone metabolism in rats. Therefore' an experiment with growing male Sprague-Dawley rats was carried out' consisting of two groups of rats fed either a copper-deficient (0.06 mg Cu/kg) or a copper-adequate diet (16 mg Cu/kg). Both groups of rats were fed identical quantities of diet by pair-feeding. copper deficiency decreased the final body weight of the rats by 5% compared to copper-adequate control rats. A severe copper-deficient state in the rats fed the copper-deficient diet was proved by a large decrease of ceruloplasmin activity in serum (by 97%) and hematological changes. For estimation of thyroid hormone metabolism' the concentrations of total and free thyroxine (T4) and triiodothyronine (T3) in serum and the activity of hepatic 5`monodeiodinase (5`D) were determined. copper-deficient rats had an increased concentration of T3 in serum' whereas the concentrations of total and free T4 as well as the activity of hepatic 5`D were not different compared with copper-adequate control rats. Therefore' the study shows that copper deficiency has only slight effects on thyroid hormone metabolism in growing rats.

Title
copper as an essential nutrient.
Author
Olivares M; Uauy R
Address
Institute of Nutrition and Food Technology' University of Chile' Santiago.
Source
Am J Clin Nutr, 63(5):791S-6S 1996 May
Abstract
Animal and human studies have shown that copper is involved in the function of several enzymes. Studies have also shown that copper is required for infant growth' host defense mechanisms' bone strength' red and white cell maturation' iron transport' cholesterol and glucose metabolism' myocardial contractility' and brain development. copper deficiency can result in the expression of an inherited defect such as Menkes syndrome or in an acquired condition. Acquired deficiency is mainly a pathology of infants; however' it has been diagnosed also in children and adults. Most cases of copper deficiency have been described in malnourished children. The most constant clinical manifestations of acquired copper deficiency are anemia' neutropenia' and bone abnormalities. Other' less frequent manifestations are hypopigmentation of the hair' hypotonia' impaired growth' increased incidence of infections' alterations of phagocytic capacity of the neutrophils' abnormalities of cholesterol and glucose metabolism' and cardiovascular alterations. Measurements of serum copper and ceruloplasmin concentrations are currently used to evaluate copper status. These indexes are diminished in severe to moderate copper deficiency; however' they are less sensitive to marginal copper deficiency. Erythrocyte superoxide dismutase and platelet cytochrome c activities may be more promising indexes for evaluating marginal copper deficiency.

Title
Auditory startle response is diminished in rats after recovery from perinatal copper deficiency.
Author
Prohaska JR; Hoffman RG
Address
Department of Biochemistry' University of Minnesota' Duluth' USA.
Source
J Nutr, 126(3):618-27 1996 Mar
Abstract
Recovery from perinatal copper deficiency was studied in female and male Sprague Dawley rats for 6 mo. Month-old offspring reared by dams on copper-deficient treatment starting d 7 of pregnancy had up to 80% reductions in regional brain copper concentrations compared with offspring from copper-supplemented dams. Liver copper concentrations and plasma ceruloplasmin diamine oxidase activities of copper-deficient rats were restored to control levels within 1 mo of nutritional repletion with dietary copper. However' brain copper concentrations' with the exception of the hypothalamus and medulla' remain lower than in controls even after 5 mo of treatment. Rats were screened for startle responses and foot splay after 1' 3 and 5 mo of repletion. Diminished auditory startle was evident in rats of both sexes at all repletion times tested' whereas tactile startle and preimpulse inhibition of tactile startle were not influenced by prior copper deficiency' suggesting auditory sensory perception abnormalities. In a separate study' postweaning male rats deprived of dietary copper for 5 wk exhibited clear signs of copper deficiency but normal acoustic startle responses and foot splay. Long-term neurochemical and behavioral abnormalities persist in rats after perinatal copper deficiency.

Title
Altered expressions of cardiac Na/K-ATPase isoforms in copper deficient
rats.
Author
Huang W; Lai CC; Wang Y; Askari A; Klevay LM; Askari A; Chiu TH
Address
Medical College of Ohio' Toledo 43699-0008' USA.
Source
Cardiovasc Res, 29(4):563-8 1995 Apr
Abstract
OBJECTIVE: The aim was to determine if copper deficiency affects the expression of Na/K-ATPase alpha isoforms in the rat heart. METHODS: copper deficiency was induced by placing weanling rats on a copper deficient diet for 4-5 weeks. Adult ventricular tissue' isolated ventricular myocytes' and brain stems of the control and deficient rats were compared for Cu' Zn-superoxide dismutase (CuZn-SOD) activity and for protein and mRNA contents of Na/K-ATPase alpha isoforms. RESULTS: In brain stem' where copper deficiency did not alter CuZn-SOD activity' mRNA and protein levels of alpha isoforms also remained unchanged. In ventricular tissue and ventricular myocytes' copper deficiency reduced CuZn-SOD activity' mRNAs of alpha 1 and alpha 2 isoforms' and the alpha 2 isoform protein. The alpha 1 isoform protein of ventricular tissue and its myocytes was marginally reduced by copper deficiency. CONCLUSIONS: In the rat ventricular tissue' oxidative stress resulting from copper deficiency (1) enhances the turnover of the more oxidant sensitive alpha 2 isoform to a greater extent than the turnover of the alpha 1 isoform; (2) regulates mRNA levels of alpha 1 and alpha 2 isoforms; and (3) contributes to the cardiomyopathy of copper deficiency.

Title
Expression of gamma-glutamylcysteine synthetase in the liver of copper-deficient rats.
Author
Chen Y; Saari JT; Kang YJ
Address
Department of Pharmacology and Toxicology' University of North Dakota School of Medicine' Grand Forks 58202' USA.
Source
Proc Soc Exp Biol Med, 210(2):102-6 1995 Nov
Abstract
copper deficiency in rats increases hepatic glutathione concentration. The present study was undertaken to determine the biochemical and molecular basis for the glutathione elevation. Weanling Sprague-Dawley rats were fed a purified diet deficient in copper (0.4 micrograms/g diet) or one containing adequate copper (5.7 micrograms/g diet) for 4 weeks. Hepatic glutathione concentration' the activity of the rate-limiting enzyme in glutathione biosynthesis' gamma-glutamylcysteine synthetase (gamma-GCS) and the relative amount of mRNA for the enzyme were determined. Hepatic glutathione concentration in copper-deficient rats was significantly elevated (6.6 vs 5.6 mumol/g). The activity of hepatic gamma-GCS was 1.6 times higher in the copper-deficient than in the copper-adequate rats (58.0 vs 35.9 nmol NADH/min.mg protein). The steady-state amount of mRNA for gamma-GCS was increased 5-fold in the copper-deficient rat liver. The findings demonstrate that the elevated hepatic glutathione concentration in copper-deficient rats results from upregulation of gamma-GCS activity. This study provides further understanding of changes in hepatic glutathione metabolism induced by copper deficiency.

Title
Feeding of excessive cystine and cysteine enhances defects of dietary copper deficiency in rats by differential mechanisms involving altered
iron status.
Author
Wan Q; Yang BS; Kato N
Address
Department of Applied Biochemistry' Faculty of Applied Biological Science' Hiroshima University' Japan.
Source
J Nutr Sci Vitaminol (Tokyo), 42(3):185-93 1996 Jun
Abstract
We have reported that excess cystine feeding exaggerates the defects of dietary copper deficiency in rats by a mechanism not involving oxidative stress and altered copper status. This study was conducted to examine whether this exacerbation is caused by a mechanism involving altered iron status and to compare the influences of cystine and cysteine feeding on the defects of copper deficiency. Male Wistar rats were fed copper-adequate or copper-deficient diet with supplementation of L-cystine or L-cysteine (2%) for 10 days or 21 days. copper-deficient diet increased heart weight' caused anemia' reduced plasma iron and elevated liver iron. These defects were exacerbated by supplemental cystine. Cysteine feeding also exacerbated the defects of dietary copper deficiency including anemia' increased heart weight' and reduced plasma iron' although cysteine feeding had no influence on liver iron concentration. Supplemental cysteine reduced apparent absorption of iron' while supplemental cystine did not. These results suggest that cystine feeding enhances the defects of copper deficiency by a mechanism involving impaired mobilization of iron from liver into blood' and that cysteine feeding enhances the defects of copper deficiency by a mechanism involving reduced intestinal absorption of iron.

Title
Regulated copper uptake in Chlamydomonas reinhardtii in response to copper availability.
Author
Hill KL; Hassett R; Kosman D; Merchant S
Address
Department of Chemistry and Biochemistry' University of California' Los
Angeles 90095-1569' USA.
Source
Plant Physiol, 112(2):697-704 1996 Oct
Abstract
A saturable and temperature-dependent copper uptake pathway has been identified in Chlamydomonas reinhardtii. The uptake system has a high affinity for copper ions (Km approximately 0.2 microM) and is more active in cells that are adapted to copper deficiency than to cells grown in a medium containing physiological (submicromolar to micromolar) copper ion concentrations. The maximum velocity of copper uptake by copper-deficient cells (169 pmol h-1 10(6) cells-1 or 62 ng min-1 mg-1 chlorophyll) is up to 20-fold greater than that of fully copper-supplemented cells' and the Km (approximately 2 x 10(2) nM) is unaffected. Thus' the same uptake system appears to operate in both copper-replete and copper-deficient cells' but its expression or activity must be induced under copper-deficient conditions. A cupric reductase activity is also increased in copper-deficient compared with copper-sufficient cells. The physiological characteristics of the regulation of this cupric reductase are compatible with its involvement in the uptake pathway. Despite the operation of the uptake pathway under both copper-replete and copper-deficient conditions' C. reinhardtii cells maintained in fully copper-supplemented cells do not accumulate copper in excess of their metabolic need. These results provide evidence for a homeostatic mechanism for copper metabolism in C. reinhardtii.

Title
Plasma diamine oxidase activities in renal dialysis patients, a human with spontaneous copper deficiency and marginally copper deficient rats.
Author
DiSilvestro RA; Jones AA; Smith D; Wildman R
Address
Ohio State University, Columbus 43210-1295, USA. disilvestro.1@osu.edu
Source
Clin Biochem, 30(7):559-63 1997 Oct
Abstract
OBJECTIVES: Intestine and kidney are generally the most concentrated sources of the copper metalloenzyme diamine oxidase (DAO). Clinically, plasma DAO activities are used to diagnose disruptions in intestinal integrity. This study determined whether DAO activities were also affected by kidney injury or copper nutritional status. DESIGN AND METHODS: Plasma DAO activities were measured in renal dialysis patients without diagnosed intestinal disease (n = 75), controls (n = 23), an adult with spontaneous copper deficiency before and after copper repletions, and in rats fed either adequate or marginal copper diets (8 or 2 mg copper/kg diet) for 7 months. RESULTS: This study found high DAO activities in renal dialysis patients and low activities during spontaneous copper deficiency. Low activities were also seen for marginally copper deficient rats. CONCLUSIONS: Tissue injury-induced elevation of DAO activities is not limited to intestinal injury, and low DAO values may be useful for assessing copper nutritional status.

Title
Effects of copper deficiency and Cu complexes on superoxide dismutase in rats.
Author
Dashti SI; Thomson M; Mameesh MS
Address
Nutrition Unit' University of Kuwait' Kuwait.
Source
Nutrition, 11(5 Suppl):564-7 1995 Sep-Oct
Abstract
The effect of dietary copper (Cu) deficiency on the antioxidant enzyme superoxide dismutase (SOD) was investigated in both erythrocyte and liver samples of 40 weanling Wistar rats. Groups were fed control (10 mg Cu/kg) or Cu-deficient (0.5 mg Cu/kg) diets for 7 wk. In this study' dietary copper deficiency did not affect growth' food intake' liver size' or hemoglobin levels. Protein concentrations were considerably decreased in the livers of the copper-deficient group compared to control groups after 7 wk. Erythrocyte SOD activity was not significantly different in copper-deficient groups. In contrast' SOD activity was significantly reduced in livers of rats consuming the Cu-deficient diet compared to controls. The in vitro SOD activities in the presence of five different macro-cyclic copper-II containing complexes with different stability constants were studied. The moderately stable copper complex increased the SOD activity in Cu-deficient liver and erythrocyte samples only at wk 7. At wk 6' a significant increase in SOD activity in liver samples only was observed. In contrast' at wk 4' no significant differences in SOD activity were observed upon addition of Cu complexes. These results suggest that the increase in SOD activity may be due to superoxide-like action or other properties of this copper complex.

Title
copper deficiency increases hepatic apolipoprotein A-I synthesis and secretion but does not alter hepatic total cellular apolipoprotein A-I mRNA abundance in rats.
Author
Hoogeveen RC; Reaves SK; Lei KY
Address
Department of Nutritional Sciences' University of Arizona' Tucson 85721' USA.
Source
J Nutr, 125(12):2935-44 1995 Dec
Abstract
This study was designed to determine whether an increase in hepatic apolipoprotein A-I (apo A-I) synthesis and mRNA abundance is responsible for the enlarged plasma apo A-I pool observed in copper-deficient rats. Weanling male Sprague-Dawley rats were divided into two dietary treatments: copper-adequate (102.2 mumol Cu/kg diet) and copper-deficient (9.0 mumol Cu/kg diet). copper deficiency resulted in a significant increase (124%) in intravascular apo A-I pool size after 6 wk of treatment. Following intraportal inJection of a flooding dose of [3H phenylalanine' in vivo hepatic apo A-I synthesis and secretion were significantly greater in the copper-deficient animals as detected by [3H phenylalanine incorporation into immunoprecipitable apo A-I isolated from liver homogenates and plasma using anti-rat apo A-I antibodies. Pulse-chase experiments using freshly isolated hepatocytes demonstrated that a significant increase (148%) in apo A-I secretion by hepatocytes derived from copper-deficient rats may have resulted from increased hepatic synthesis rather than altered intracellular degradation of apo A-I. Hepatic total cellular apo A-I mRNA abundance was not altered by copper deficiency when expressed per microgram of RNA. Thus' the enhanced hepatic apo A-I synthesis' observed in copper-deficient cells' may have resulted from alterations in post-transcriptional and translational processes.

 

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