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Title
copper deficiency: interaction with high-fructose and high-fat
diets in rats.
Author
Wapnir RA; Devas G
Address
Department of Pediatrics' North Shore University Hospital--Cornell
University Medical College' Manhasset' NY 11030.
Source
Am J Clin Nutr, 61(1):105-10 1995 Jan
Abstract
The purpose of this study was to investigate whether a high fat
intake would potentiate an excess of fructose in the diet of
rats to alter energy metabolism and worsen the nutritional status
for copper. Weanling male rats were fed diets with 45% fat and
20% cornstarch' 45% fat and 20% fructose' 5% fat and 60% cornstarch'
or 5% fat and 60% fructose for 3 wk' with either sufficient (+)
or deficient (-) amounts of copper. copper deficiency' as demonstrated
by low plasma copper and ceruloplasmin' caused a decrease of
liver' heart' and testes copper; a decline of liver and heart
zinc; and an increase of hepatic iron. High-fat diets reduced
liver glucose-6-phosphate dehydrogenase (G6PDH) and' to a lesser
extent' glycerophosphate dehydrogenase (GPDH). The interaction
between high-fat and high-fructose diets' superimposed on copper
deficiency' resulted in a lowering of G6PDH' GPDH' and malic
enzyme. These results support the hypothesis that a high fat
ingestion becomes an aggravating stress factor' which' in combination
with a high-fructose intake in a copper-deficient diet' adversely
alters key organ mineral content' with detrimental effects on
copper nutritional status and intermediary metabolism.
Title
Trace elements in long-term total parenteral nutrition
Author
Itokawa Y
Address
Graduate School of Medicine' Kyoto University.
Source
Nippon Rinsho, 54(1):172-8 1996 Jan
Abstract
Deficiency symptoms of trace elements developed in patients receiving
long-term total parenteral nutrition (TPN) are as follows. [Zinc
deficiency : moist eczematoid dermatitis and alopetia are occurred
in patients receiving TPN which not containing zinc. Plasma zinc
level was very low. The response to intravenous zinc therapy
is striking. [copper deficiency : anemie and neutropenia caused
in patients receiving TPN which not containing copper. These
abnormalities disappeared after copper therapy. [Manganese deficiency
: bone changes which thought to be due to manganese deficiency
was observed in patient receiving TPN. [Selenium deficiency :
dilated cardiomyopathy resembles to Keshan disease was occurred
in patients receiving TPN for long term. [Chromium deficiency
: TPN induced chromium deficiency developed characterized by
peripheral neuropathy and glucose intolerance. [Molybudenum deficiency
: Amino acid intolerance due to molybudenum deficiency is occurred
in patients receiving TPN. Requirement of trace elements for
human adults from TPN estimated as follows. zinc: 3-4 mg/day'
copper: 0.02-0.05 mg/day' iron: 1-2 mg/day' manganese: 0.15-0.80
mg/day' selenium: 0.02-0.05 mg/day' chromium: 0.01-0.015 mg/day'
molybudenum: 0.075-0.250 mg/day and iodine: 0.070-0.140 mg/day.
Title
copper-related blood indexes in kidney dialysis patients.
Author
Emenaker NJ; DiSilvestro RA; Nahman NS Jr; Percival S
Address
Department of Human Nutrition and Food Management' Ohio State
University' Columbus 43210-1295' USA.
Source
Am J Clin Nutr, 64(5):757-60 1996 Nov
Abstract
Previous work has suggested that kidney hemodialysis patients
could be at risk for either moderate copper deficiency or copper
toxicity. The present study examined copper-related blood indexes
in subJects undergoing hemodialysis treatments with membranes
that are not copper-based' in subJects undergoing chronic ambulatory
peritoneal dialysis (CAPD)' and in control subJects. Both dialysis
groups had low plasma copper and ceruloplasmin activities. This
occurred despite high plasma interleukin 6 concentrations' a
situation that usually elevates plasma ceruloplasmin and copper
values. CAPD and hemodialysis subJects had low ratios of ceruloplasmin
activity to immunoreactive protein' and low ratios of plasma
copper to ceruloplasmin protein. Both are signs of copper deficiency.
In contrast' copper-containing erythrocyte superoxide dismutase
(SOD) activities were high in hemodialysis subJects and showed
a nonsignificant trend toward high values in CAPD subJects. Blood
mononuclear cell copper contents were highly variable within
each group' and there were no significant differences between
groups. In conclusion' ceruloplasmin-related indexes in kidney
dialysis patients not dialyzed with copper-based membranes suggested
a tendency toward moderate copper deficiency. However' this contention
could not be confirmed by erythrocyte SOD activity or mononuclear
cell copper measurements.
Title
Degradation of plastocyanin in copper-deficient Chlamydomonas
reinhardtii. Evidence for a protease-susceptible conformation
of the apoprotein and regulated proteolysis.
Author
Li HH; Merchant S
Address
Department of Chemistry and Biochemistry' University of California
at Los Angeles 90095-1569' USA.
Source
J Biol Chem, 270(40):23504-10 1995 Oct 6
Abstract
In the green alga Chlamydomonas reinhardtii' the copper-dependent
accumulation of plastocyanin is effected via the altered stability
of the protein in copper-deficient versus copper-sufficient medium
(t1/2) < 20 min versus several hours). To understand the mechanism
of plastocyanin degradation in vivo' the purified apoprotein
was characterized relative to the holoprotein with respect to
conformation and protease susceptibility. Circular dichroism
spectroscopy revealed that the apoprotein in solution did not
display the characteristic secondary structure displayed by the
native or reconstituted holoprotein. The apoprotein was also
susceptible to digestion in vitro by chymotrypsin whereas the
holoprotein was resistant. High ionic conditions' which stabilize
the folded structure of apoplastocyanin' also inhibit its degradation
by chymotrypsin. These results suggest that one explanation for
plastocyanin degradation in copper-deficient cells in vivo might
be the increased susceptibility of the apo form to a lumenal
protease. Since apoplastocyanin is a normal biosynthetic intermediate
for the formation of holoplastocyanin' the increased susceptibility
of apoplastocyanin to proteolysis implies that degradative and
biosynthetic activities would compete for the same substrate.
However' characterization of an apoplastocyanin-accumulating
mutant suggests that a plastocyanin-degrading protease is active
only in copper-deficient cells. Thus' apoplastocyanin is rapidly
degraded in copper-deficient cells' whereas its maJor fate in
copper-supplemented cells is holoplastocyanin formation.
Title
copper binding to mouse liver S-adenosylhomocysteine hydrolase
and the effects of copper on its levels.
Author
Bethin KE; Cimato TR; Ettinger MJ
Address
Department of Biochemistry' State University of New York at Buffalo
14214' USA.
Source
J Biol Chem, 270(35):20703-11 1995 Sep 1
Abstract
The dissociation constant and stoichiometry of copper binding
to mouse liver S-adenosylhomocysteine hydrolase (SAHH) was determined
as part of characterizing the possible roles of SAHH in copper
metabolism. copper (64Cu(II)) binding was measured by an ultrafiltration
method in the presence of EDTA as a competing ligand. The KD
was 3.9 +/- 0.7 x 10(-16) M' and the stoichiometry was one g
atom of copper per 48-kDa subunit. Western blots indicated that
the liver contains approximately 12 times more SAHH than the
kidney' which in turn contains approximately 5 times more SAHH
than the brain. The high concentration and copper affinity of
SAHH in the liver may contribute to the liver`s ability to preferentially
accumulate copper' and the low levels of SAHH in the brain may
contribute to the sensitivity of the brain to copper deficiency.
The effects of genetic defects of copper metabolism and copper
deficiency on SAHH were also determined. Normal SAHH levels were
detected in brindled mouse liver' kidney' and brain. However'
SAHH from brindled mouse liver eluted abnormally from phenyl
Superose columns implying an effect of the brindled mouse defect
on SAHH protein structure. Hepatic cytosols from the toxic milk
mouse contained approximately 42% the amount of SAHH detected
in controls' and hepatic levels of SAHH were also decreased by
approximately 45% in copper-deficient mice. The binding properties
of SAHH and the effects of abnormal states of copper metabolism
on its levels are consistent with significant roles for SAHH
in normal and abnormal copper metabolism. SAHH may have roles
in regulating tissue copper levels and the distribution of intracellular
copper.
Title
Antioxidant defense mechanisms in the male rat: interaction with
alcohol' copper' and type of dietary carbohydrate.
Author
Fields M; Lure MD; Lewis CG
Address
Beltsville Human Nutrition Research Center' USDA' ARS' MD 20705'
USA.
Source
Alcohol, 12(1):65-70 1995 Jan-Feb
Abstract
The activities of enzymes participating in cellular protection
against free radical reactions were measured in hepatic tissues
from copper-adequate and copper-deficient rats fed fructose or
starch-based diets. Half of the rats consumed 20% ethanol in
their drinking water. The consumption of ethanol depressed growth
rate' reduced hematocrit' and hepatic copper concentration. Feed
efficiency was greatly depressed by ethanol. Mortality due to
copper deficiency occurred in fructose-fed rats and in starch-fed
rats that drank ethanol. Ethanol had no effect on superoxide
dismutase (SOD)' glutathione peroxidase (GSH-Px)' or catalase.
In contrast' copper deficiency reduced SOD and fructose feeding
depressed catalase activity. GSH-Px was not affected by either
the type of dietary carbohydrate' copper' or ethanol. Taken together'
these data suggest that additional mechanisms to antioxidant
defense systems are responsible for the metabolic changes that
occur during the interactions between ethanol low copper and
dietary carbohydrates.
Title
copper deficiency reduces interleukin-2 (IL-2) production and
IL-2 mRNA in human T-lymphocytes.
Author
Hopkins RG; Failla ML
Address
Department of Food' Nutrition & Food Service Management'
The University of North Carolina Greensboro' 27412-5001' USA.
Source
J Nutr, 127(2):257-62 1997 Feb
Abstract
Although dietary copper (Cu) deficiency has been associated with
decreased production of interleukin-2 (IL-2) by activated splenic
mononuclear cells in rodent models' the basis for this relationship
and its relevance for humans remain unknown. To Address
these matters' we have developed an in vitro model of cellular
copper deficiency by treating Jurkat' a human T-lymphocyte cell
line' with low concentrations of 2'3'2-tetraamine (2'3'2-tet)'
a high affinity copper chelator. Exposure to 5-20 micromol/L
2'3'2-tet for 35 h decreased cell copper and the activity of
Cu'Zn-superoxide dismutase (Cu'Zn-SOD) by 30-40% and IL-2 production
by 60-70% in cultures activated with phytohemagglutinin and phorbol
myristate acetate. Similarly' IL-2 mRNA levels were 40-70% lower
in chelator-treated cells than in untreated cells at 3-12 h after
activation. In contrast' chelator treatment had no significant
effect on cell viability' growth' protein synthesis or mitochondrial
activity. The presence of a slight molar excess of copper' but
not zinc or iron' during exposure to 2'3'2-tet prevented the
chelator-induced decrease in Cu'Zn-SOD activity and the reductions
in IL-2 mRNA and bioactivity. Moreover' binding of diferric transferrin
(Tf) and cellular uptake of Tf-59Fe by Jurkat cells were not
increased by 2'3'2-tet' indicating that chelator-treated cells
were not iron deficient. Finally' incubation of human peripheral
blood mononuclear cells (PBMC) with 2'3'2-tet decreased mitogen-induced
IL-2 production by 50% compared with untreated controls. These
data indicate that a decline in copper status decreases IL-2
production by activated human T-cells due to reduced synthesis
and/or stability of IL-2 mRNA.
Title
Platelet aggregation and adhesion during dietary copper deficiency
in rats.
Author
Lominadze DG; Saari JT; Miller FN; Catalfamo JL; Justus DE; Schuschke
DA
Address
Center for Applied Microcirculatory Research' University of Louisville'
KY 40292' USA.
Source
Thromb Haemost, 75(4):630-4 1996 Apr
Abstract
The role of dietary copper deficiency in platelet-to-endothelial
cell adhesion and in platelet-to-platelet aggregation was studied
in vitro. Platelets were obtained from male' weanling Sprague-Dawley
rats fed purified diets which were either copper-adequate (CuA'
6.3 micrograms copper/g of diet) or copper-deficient (CuD' 0.3
microgram/g of diet) for 4 weeks. The platelet adhesion study
was performed by adding CuA or CuD platelets either suspended
in homologous plasma or in Tyrode buffer salt solution (TBSS)
to cultured rate endothelial cells. After a one hour incubation
at 37 degrees C non-adhered platelets were removed and counted
in a microcytometer. Platelet aggregation in platelet rich plasma
(PRP) samples was induced by adding ADP (2 x 10(-4)M) and measured
in a turbidometric aggregometer. The content of von Willebrand
factor (vWF) in platelets and in plasma and the content of fibrinogen
in platelets was determined. Platelet adhesion to rat endothelial
cells was significantly lower for platelets from CuD rats than
for platelets from CuA rats. ADP induced platelet aggregation
from CuD rats was significantly higher than platelet aggregation
from CuA rats. The content of vWF in platelets and in plasma
from CuD rats was significantly lower than in platelets and plasma
from CuA rats. However' the amount of fibrinogen in platelets
from ++CuD rats was about 4-fold higher than that in platelets
from CuA rats while the plasma fibrinogen was lower in CuD rats
than in CuA rats. These studies illustrate that copper deficiency
diminishes platelet adhesion to endothelial cells but increases
platelet aggregability. The results suggest that these physiological
alterations may be the result of decreased platelet vWF and increased
platelet fibrinogen during dietary copper deficiency.
Title
Hypothesis: the possible role of magnesium and copper deficiency
in retinopathy of prematurity.
Author
Caddell JL
Address
Department of Pediatrics' Thomas Jefferson University' Philadelphia'
USA.
Source
Magnes Res, 8(3):261-70 1995 Sep
Abstract
This hypothesis states that magnesium and copper (Cu) deficiency
as well as high arterial oxygen pressure may contribute to the
pathogenesis of retinopathy of prematurity (ROP)' a maJor cause
of blindness in very low birthweight preterm infants. Infants
at highest risk have severe respiratory distress with hypoxia
and require prolonged oxygen supplements. The retina is a multilayer
sheet of neural tissue very rich in polyunsaturated fatty acids
(PUFAs)' oxygen' and mitochondria' with the highest oxygen consumption
of all body tissues. Oxygen free radicals which are generated
during metabolism cause lipid peroxidation of the PUFA-rich membranes'
impairing retinal function. Magnesium and copper deficiencies
provide less protection from oxidative inJury which damages neurosensory
tissue critical for photodetection. Protective antioxidant enzyme
activity is reduced in magnesium and copper deficiency. There
is some evidence for a raised level of vasoconstrictor thromboxane
A2 (TXA2) in respect to vasodilator prostacyclin (PGI2)' which
would promote vasoconstriction. Deficiency of magnesium and of
copper increase synthesis of TXA2 and decreases synthesis of
PGI2. Sustained vasoconstriction leads to vascular occlusion'
retinal ischaemia' reactive proliferation of retinal vasculature'
and the final stages of ROP. Abundant magnesium and copper may
protect the retina from developing ROP.
Title
Benfluorex, a hypotriglyceridemic drug, reduces lipid peroxidation
and alleviates adverse metabolic complications of copper deficiency.
Author
Fields M; Lewis CG
Address
USDA, ARS, Beltsville Human Nutrition Research Center, Metabolism
and Nutrient Interactions Laboratory, Beltsville, Maryland 20705,
USA.
Source
Nutrition, 13(10):895-9 1997 Oct
Abstract
The pathologies associated with copper deficiency in rats fed
fructose may be induced, in part, by hypertriglyceridemia and
lipid peroxidation. Reducing triacylglycerol levels in plasma
may result in lowering lipid peroxidation, which in turn could
ameliorate metabolic effects resulting from the combination of
fructose feeding and copper deficiency. Benfluorex, a hypolipidemic
factor able to reduce hypertriglyceridemia, was administered
to weanling male rats fed either copper-deficient (0.6 microgram
Cu/g) or adequate (6.0 micrograms Cu/g) diets containing fructose
as the sole dietary carbohydrate. In copper-deficient rats, benfluorex
(50 micrograms.kg-1.d-1) reduced plasma triacylglycerols from
45 to 31 mg/dL, reduced lipid peroxidation by approximately 50%,
and prevented the enlargements of heart and liver size and the
atrophy of the pancreas, and ameliorated anemia. It is suggested
that lipid peroxidation associated with hypertriglyceridemia
may be responsible for the pathologies induced by the combination
of fructose consumption and copper deficiency.
Title
[Zinc intoxication dogs with simultaneous zinc deficiency--an
expanded case study
Author
Meiser H; Schulz R
Address
Institut f ur Pharmakologie' Toxikologie und Pharmazie' Tier
arztliche Fakult at der Ludwig-Maximilians-Universit at M unchen.
Source
Berl Munch Tierarztl Wochenschr, 110(7-8):284-7 1997 Jul-Aug
Abstract
A dachshund suffered from vomitus' anorexia' apathy' and anemia.
A metal button consisting of brass (alloy of copper and zinc)
was diagnosed in the stomach and was removed. Blood analysis
revealed an elevated level of zinc (10.7 micrograms/ml) associated
with a low copper concentration (0.02 microgram/ml). This apparently
paradoxical finding of copper deficiency despite of copper exposition
(brass button) caused us to determine the diaminoxidase activity
in serum' representing an indicator for the copper accumulating
ceruloplasmin. The enzyme activity was found to be decreased.
The case study brings to mind the mutual interaction between
zinc and copper. Apparently' a copper deficiency is not necessarily
due to a reduced supply of copper. Moreover' as shown by further
investigations' an attenuated diaminoxidase activity represents
an important parameter to diagnose a copper deficient state.
Title
copper deficiency alters isomyosin types and levels of laminin'
fibronectin and cytochrome c oxidase subunits from rat hearts.
Author
Liao Z; Allred J; Keen CL; McCune SA; Rucker RB; Medeiros DM
Address
Department of Human Nutrition and Food Management' Ohio State
University' Columbus 43201-1295' USA.
Source
Comp Biochem Physiol B Biochem Mol Biol, 111(1):61-7 1995 May
Abstract
The relative amounts of cardiac proteins such as laminin' fibronectin'
cytochrome c oxidase' and isomyosin types were studied by gel
electrophoresis and Western blotting in control and copper-deficient
Sprague-Dawley rats of both sexes fed their respective diets
from weanling for 3 weeks. Isomyosin types appeared to shift
from V1 to greater levels of V3 in copper deficient rats for
both genders. Male copper deficient rats had increased cardiac
levels of fibronectin' decreased laminin levels' cardiac hypertrophy
and anemia. Both male and female rats fed copper-deficient diet
had lower levels of cytochrome c oxidase (CCO) subunit IV' and
low liver copper' and high heart-to-body weight ratios compared
with their respective controls.
Title
Hepatic iron overload may contribute to hypertriglyceridemia
and hypercholesterolemia in copper-deficient rats.
Author
Fields M; Lewis CG
Address
Metabolism and Nutrient Interactions Laboratory' Beltsville Human
Nutrition Research Center' US Department of Agriculture' Agricultural
Research Service' MD 20705' USA.
Source
Metabolism, 46(4):377-81 1997 Apr
Abstract
The present study was conducted in order to determine whether
hepatic iron retention in rats fed a copper-deficient diet containing
fructose is associated with hypertriglyceridemia and hypercholesterolemia'
and whether a reduction of iron intake will prevent elevation
of blood triglycerides and cholesterol. Rats were fed from weaning
either a copper-deficient (0.6 microgram Cu/g) or copper-adequate
(6.0 micrograms Cu/g) diet for 4 weeks. Half the rats consumed
either an adequate level of iron (50 micrograms Fe/g) or a low
level (17 micrograms Fe/g). Reduction of iron intake reduced
blood levels of both triglycerides and cholesterol in rats fed
a copper-deficient diet containing fructose. In addition' hepatic
lipid peroxidation was also decreased. The combination of high
iron' low copper' and fructose may be responsible for increased
levels of risk-factor metabolites associated with heart disease.
Title
Responses of insulin to oral glucose and fructose loads in marginally
copper-deficient rats fed starch or fructose.
Author
Fields M; Lewis CG; Lure MD
Address
Beltsville Human Nutrition Research Center' USDA' MD 20705' USA.
Source
Nutrition, 12(7-8):524-8 1996 Jul-Aug
Abstract
The purpose of this study was to assess the effects of dietary
fructose either alone or in combination with marginal copper
deficiency in weanling male rats exposed to their respective
diets for only 2 wk. This short duration of exposure to inadequate
copper intake prevents progressive morbidity brought about by
increasing periods of exposure to dietary copper deprivation.
Weanling male rats were fed a copper-deficient (0.6 microgram
Cu/g) or a copper-adequate (6.0 micrograms Cu/g) diet containing
62% fructose or 62% starch for 2 wk. Either an oral glucose or
an oral fructose tolerance test was conducted after an overnight
fast. Insulin levels were elevated by either oral glucose or
oral fructose at fasting and at 30 min postload in rats fed fructose
compared with those fed starch. Despite high levels of plasma'
insulin blood glucose was not reduced. Marginal copper deficiency
had no effect on either plasma insulin or blood glucose. Data
identify fructose as the sole agent responsible for inducing
adverse changes in glucose metabolism. Two weeks of fructose
consumption was sufficient to produce these changes. |
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