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Title
Decreased nuclear encoded subunits of cytochrome c oxidase and
increased copper, zinc-superoxide dismutase activity are found
in
cardiomyopathic human hearts.
Author
Liebes R; Medeiros DM
Address
Department of Human Nutrition and Food Management, The Ohio State
University, Columbus 43210-1295, USA.
Source
Int J Cardiol, 62(3):259-67 1997 Dec 19
Abstract
Mineral concentrations, copper, zinc-superoxide dismutase and
cytochrome c oxidase subunits in human cardiomyopathic heart
explants
were compared with noncardiomyopathic hearts from autopsy subjects.
Iron was reduced in cardiomyopathic hearts, but the zinc:iron
ratio was
higher in cardiomyopathic hearts. copper, zinc-superoxide dismutase
activity was increased in cardiomyopathic human hearts compared
to the
noncardiomyopathic hearts. In a subsample of specimens analyzed,
the
nuclear encoded subunits of cytochrome c oxidase were diminished
in the
cardiomyopathic hearts. The decreases have been observed in rodents
fed
copper-deficient diets. However, in this study heart copper levels
did
not differ by disease status.
Title
Alterations of rat hepatoma cell genomes induced by copper deficiency.
Author
Renault E; Deschatrette J
Address
Unit]e 347 de l'Institut National de la Sant]e et de la Recherche
Medical, Le Kremlin-Bic^etre, France.
Source
Nutr Cancer, 29(3):242-7 1997
Abstract
copper deficiency imposed on a variant rat hepatoma cell line
inhibits
cell growth and results in genesis of stable well-differentiated,
tumorigenic revertants. The treatment caused a substantial increase
in
DNA content (up to 20%) of G1 and G2/M cells and inhibition of
cell
proliferation. This phenomenon was correlated with an enhancement
of
DNA replication. The excess DNA was unstable and rapidly lost
with
reinitiation of cell growth and mitosis. Minute and double-minute
extrachromosomal material was detected by metaphase analysis,
suggesting widespread DNA amplification in copper-deficient conditions.
Although transitory, these genetic events were associated with
genesis
of drug-resistant cells and induction of tumorigenicity of the
variant
hepatoma cells. The data reveal a novel aspect of the consequences
of
trace element deficiency.
Title
Role of intracellular SOD in oxidant-induced inJury to normal
and
copper-deficient cardiac myocytes.
Author
Sarvazyan N; Askari A; Klevay LM; Askari A; Huang WH
Address
Department of Pharmacology' Medical College of Ohio' Toledo 43699.
Source
Am J Physiol, 268(3 Pt 2):H1115-21 1995 Mar
Abstract
Previous studies have shown that susceptibilities of hepatocytes
and
endothelial cells to H2O(2)-induced inJury are altered by changes
in
the intracellular activity of Cu'Zn-containing superoxide dismutase
(CuZn-SOD). To evaluate the role of intracellular CuZn-SOD in
oxidant-induced inJury to rat cardiac myocytes' cells with reduced
CuZn-SOD activity but normal ATP content were either isolated
from the
hearts of adult copper-deficient rats or obtained by treatment
of
normal isolated adult myocytes with diethyldithiocarbamate. These
myocytes and controls with normal CuZn-SOD activity were exposed
to
either reagent H2O2 or oxidants generated by extracellular glucose
oxidase plus glucose or xanthine oxidase plus xanthine. It was
shown
that myocytes with CuZn-SOD activities reduced by 70-90% were
equally
susceptible to H2O2 and the two oxidant-generating systems as
the
control myocytes. The findings suggest that in adult cardiac
myocytes'
in contrast to the situation in some other cells' intracellular
CuZn-SOD may not have a significant defensive role against acute
H2O(2)-induced inJury. The possibility remains' however' that
changes
in the activity of this enzyme' e.g.' in copper deficiency' may
be
relevant to the ability of myocytes to cope with chronic oxidative
stress resulting from imbalance between intracellular oxygen
radical-generating and -scavenging systems.
Title
copper deficiency-induced anemia and neutropenia secondary to
intestinal malabsorption.
Author
Hayton BA; Broome HE; Lilenbaum RC
Address
Department of Medicine' University of California' San Diego 92103-8421.
Source
Am J Hematol, 48(1):45-7 1995 Jan
Abstract
A patient with a history of partial gastrectomy presented with
severe
anemia' neutropenia' intestinal malabsorption' and was found
to be
severely copper-deficient. The anemia and neutropenia corrected
promptly with the administration of intravenous cupric chloride.
This
case suggests that partial gastrectomy with or without intestinal
malabsorption can result in copper deficiency and should be considered
in differential diagnosis of severe anemia and neutropenia.
Title
The effects of copper deficiency with or without high dietary
iron or
molybdenum on immune function of cattle.
Author
Ward JD; Gengelbach GP; Spears JW
Address
Department of Animal Science and Interdepartmental Nutrition
Program'
North Carolina State University' Raleigh 27695-7621' USA.
Source
J Anim Sci, 75(5):1400-8 1997 May
Abstract
Two experiments were conducted to determine the effects of Cu
deficiency with or without high dietary Mo or Fe on the specific
immunity of calves. In Exp. 1' calves from 38 bred heifers' fed
corn
silage-based experimental diets from the last third of gestation
until
the calves were weaned' were used. Dietary treatments were control
(no
supplemental Fe' Mo' or Cu)' 600 mg of supplemental Fe/kg of
DM' 5 mg
of supplemental Mo/kg of DM' and 10 mg of supplemental Cu/kg
of DM. In
Exp. 2' 18 Holstein bull calves were fed commercial milk replacer
low
in Cu for 49 d and then fed semipurified diets containing approximately
1.1 mg of Cu/kg of DM or diets supplemented with 5 mg of Mo or
10 mg of
Cu per kilogram of DM for 126 d. Feeding diets not supplemented
with Cu
resulted in severe Cu deficiency in both experiments. During
Exp. 1'
control calves had higher (P < .10) secondary antibody response
to pig
erythrocytes than Cu-' Mo-' and Fe-supplemented calves. During
Exp. 2'
in vitro Cu supplementation decreased (P < .01) lymphocyte
blastogenic
response. In vivo cell-mediated response to phytohemagglutinin
was
decreased (P < .10) by Cu supplementation during Exp. 1 but
was
increased (P < .10) by Cu and Mo supplementation during Exp.
2. copper
deficiency and Cu deficiency coupled with high dietary Mo or
Fe
produced inconsistent immune function responses' indicating that
Cu
deficiency may not affect specific immune function of calves.
Title
[copper--biochemistry, metabolism and physiologic function
Author
Dastych M
Address
Odd elen]i klinick]e biochemie FN, Brno-Bohunice.
Source
Cas Lek Cesk, 136(21):670-3 1997 Nov 5
Abstract
The submitted paper presents contemporary knowledge of the
biochemistry, metabolism and biological function of copper, an
essential trace element. The causes of copper deficiency, its
clinical
and laboratory manifestations and its diagnosis. Pathophysiology,
clinical and laboratory manifestations and diagnosis of Wilson's
disease.
Title
Effect of molybdenum-induced copper deficiency on in vivo and
in vitro
measures of neutrophil chemotaxis both before and following an
inflammatory stressor.
Author
Arthington JD; Spell AR; Corah LR; Blecha F
Address
Department of Animal Sciences and Industry' Kansas State University'
Manhattan 66506' USA.
Source
J Anim Sci, 74(11):2759-64 1996 Nov
Abstract
Twelve Angus x Hereford heifers (avg wt = 183.6 kg) were allotted
by
initial liver copper (Cu) concentrations into one of two treatments.
Control (n = 6) heifers were fed a basal diet supplemented to
provide a
dietary Cu level of 10 ppm. Molybdenum (Mo)-induced Cu-deficient
heifers (n = 6) were fed an identical basal diet supplemented
with
sodium molybdate (Cu:Mo ratio = 1:2.5)' with dietary sulfur at
.3% of
the total diet. Dietary treatments were delivered for 120 d'
at which
time Mo-supplemented heifers were considered Cu-deficient (286
and 49
ppm liver Cu for control and Mo-induced Cu-deficient' respectively).
Peripheral blood neutrophils were enumerated both before and
after the
administration of an inflammatory stressor' a subcutaneous inJection
(1.5 mL) of Freund`s complete adJuvant. In vitro and in vivo
measures
of neutrophil chemotaxis were evaluated and the expression of
two
adhesion molecules' CD18 and L-selectin' were analyzed by flow
cytometric procedures. Molybdenum-induced Cu deficiency increased
(P <
.01) the number of peripheral blood neutrophils; however' in
vitro
neutrophil chemotaxis was not affected. In vivo neutrophil chemotaxis
tended (P < .08) to be increased in Mo-induced Cu-deficient
heifers
(1.55 vs 2.26 x 10(6) cells/ sponge for control and Mo-supplemented'
respectively). No differences in CD18 or L-selectin expression
were
detected between treatments. However' CD18 expression was decreased
(P
< .05) in both treatments following adJuvant inJection. These
data
suggest that Mo-induced Cu deficiency results in an increase
in
peripheral blood neutrophil number' without altering chemotactic
ability and adhesion molecule expression.
Title
Anemia in copper-deficient rats: role of alterations in erythrocyte
membrane fluidity and oxidative damage.
Author
Rock E; Gueux E; Mazur A; Motta C; Rayssiguier Y
Address
Centre de Recherche en Nutrition Humaine' Institut National de
Recherche Agronomique' Theix' St-Gen`es-Champanelle' France.
Source
Am J Physiol, 269(5 Pt 1):C1245-9 1995 Nov
Abstract
This study was designed to make precise the nature and the mechanism
of
the anemia induced by dietary copper (Cu) deficiency. Male Wistar
rats
were pair fed from weanling for 6 wk either a Cu-deficient or
a control
diet. The reduced red blood cell (RBC) 51Cr survival indicates
an
increased destruction of RBC during Cu deficiency.
1'6-Diphenyl-1'3'5-hexatriene fluorescence polarization studies
revealed an increase in the fluidity of erythrocyte membranes
from
deficient rats. The reduced cholesterol-to-phospholipid ratio
was
consistent with the increased fluidity. Other results indicate
an
increased vulnerability of RBC to hemolysis in dilute hydrogen
peroxide
and an increased formation of lipid peroxidation products. Before
exposure to free radical stress' electron spin resonance studies
in
intact RBC revealed decreased correlation time of 16-doxyl-stearic
acid' confirming a more fluid membrane in RBC from Cu-deficient
rats.
After in vitro peroxidation' RBC from Cu-deficient rats showed
a more
ordered state of membrane lipids compared with controls. Together'
these studies demonstrate the hemolytic nature of the anemia.
The
shortened survival of erythrocytes apparently results from changes
in
membrane fluidity and enhanced susceptibility to peroxidation.
Title
copper deficiency and heart disease: molecular basis, recent
advances
and current concepts.
Author
Nath R
Address
Department of Experimental Medicine and Biotechnology, Postgraduate
Institute of Medical Education and Research, Chandigarh, India.
Source
Int J Biochem Cell Biol, 29(11):1245-54 1997 Nov
Abstract
copper is an essential trace element and has profound influence
on
cardiac myopathy and heart metabolism. Dietary Cu restriction
in rats
results in cardiomyopathy, and affects the integrity of the basal
lamina of cardiac myocytes and capillaries. Decreased levels
of delta
subunits of ATP synthetase and nuclear encoded subunits of cytochrome
oxidase system have been observed. Alteration in expression of
glutathione peroxidase and catalase in heart and liver in Cu
deficiency
(Cu-) has been noted involving both transcriptional and post
transcriptional mechanisms. A short description of two genetically
inherited disorders of Cu metabolism, i.e. Wilson's disease and
Menkes'
disease, and Indian childhood cirrhosis (environmental and/or
genetic)
have been included to illustrate that advances in the knowledge
of Cu
cellular transport gives a better understanding of the molecular
basis
of the pathophysiology of these diseases. Menkes' disease, a
human
model of defective Cu transport and Cu- has shown many pathological
changes, similar to those of heart disease in Cu-. The recent
cloning
of four genes of putative Cu pumping ATPases (Cu-ATPases) from
widely
different sources, i.e. two from Enterococcus hirae and one each
from
Wilson's and Menkes disease patients (which are defective in
Cu
transport and metabolism), has opened a new chapter in the study
of Cu
cellular transport and metabolism. The encoded gene products,
i.e.
Cu-ATPases, show extensive homology and are members of a new
class of
ATP-driven Cu pumps involved in regulation of cellular Cu. Further,
Cu
transport by Cop B-ATPase (E. hirae) in membrane vesicles and
in
isolated rat liver plasma membrane has provided biochemical evidence
of
its role in ATP-driven Cu transport. In this short review I have
critically examined the current evidence of the molecular basis
of the
pathophysiology of cardiomyopathy in Cu- and, have indicated
the
possible role of P-type Cu ATPase which may be one of the obligatory
factors contributing to cardiomyopathy in experimental animals
and
probably humans. Experimental verification of this hypothesis
will be
the aim of future studies.
Title
Characterization of antineutrophil antibodies in patients with
neutropenia associated with nutritional copper deficiency.
Author
Higuchi S; Hirashima M; Nunoi H; Higashi A; Naoe H; Matsuda I
Address
Department of Pediatrics' National Saishunso Hospital' Kumamoto'
Japan.
Source
Acta Haematol, 94(4):192-5 1995
Abstract
Six antineutrophil antibody (ANA)-positive patients with copper
deficiency were classified into two groups; those with (group
A' n = 3)
and those without (group B' n = 3) neutropenia. The percent binding
of
ANA for normal peripheral neutrophils was similar in both groups
(83.5
+/- 7.2 vs. 79.1 +/- 10.5%). The percent binding of sera to cultured
promyelocytic leukemia cells (HL-60) was increased in group A
(from 3.7
+/- 3.2 to 12.2 +/- 2.3%) but not in group B (from 65.3 +/- 21.7
to
40.7 +/- 6.3%) after stimulation of HL-60 with DMSO. The stimulated
HL-60 cells expressed CD 16 and CD 11b antigens. In the presence
of
monoclonal antibody for CD 16' the titer of ANA was nil in group
A and
unchanged in group B. Thus' ANA of patients with neutropenia
may
recognize mainly the CD 16 antigen' the Fc gamma receptor III
of
neutrophils.
Title
Comparative nutrition of iron and copper.
Author
Winzerling JJ; Law JH
Address
Department of Biochemistry' and the Center for Insect Science'
University of Arizona' Tucson 85721' USA.
Source
Annu Rev Nutr, 17():501-26 1997
Abstract
The suggestion from nutritional studies with mammals of a link
between
iron and copper metabolism has been reinforced by recent investigations
with yeast cells. Iron must be in the reduced ferrous (FeII)
state for
uptake by yeast cells' and reoxidation to ferric (FeIII) by a
copper
oxidase is part of the transport process. Thus' yeast cells deficient
in copper are unable to absorb iron. In an analogous way' animals
deficient in copper appear to be unable to move FeII out of cells'
probably because it cannot be oxidized to FeIII. Invertebrate
animals
use copper and iron in ways very similar to vertebrates' with
some
notable exceptions. In the cases where vertebrates and invertebrates
are similar' the latter may be useful models for vertebrate metabolism.
In cases where they differ (e.g. predominance of serum ferritin
in
insects' oxygen transport by a copper protein in many arthropods'
central importance of phenoloxidase' a copper enzyme in arthropods)'
the differences may represent processes that are exaggerated
in
invertebrates and thus more amenable to study in these organisms.
On
the other hand' they may represent processes unique to invertebrates'
thus providing novel information on species diversity.
Title
The effects of copper deficiency on human lymphoid and myeloid
cells:
an in vitro model.
Author
Tong KK; Hannigan BM; McKerr G; Strain JJ
Address
Cancer and Ageing Research Group' University of Ulster' Coleraine.
Source
Br J Nutr, 75(1):97-108 1996 Jan
Abstract
Cu has long been known to influence immune responses. An in vitro
model
system was established in which human myeloid (HL-60)' B-lymphoid
(RaJi) and T-lymphoid (Molt-3) cell lines could be grown in culture
media of varying Cu levels. Initially Cu was removed from the
medium by
dialysis of fetal calf serum against a metal-ion chelator' minor
depletion of other trace metals being obviated by repletion with
appropriate metal salts. The growth rate of HL-60 was significantly
(P
< 0.05) inhibited by 72 h Cu depletion. Molt-3 cells required
a longer
period' up to 144 h' in Cu-depleted medium before growth was
impaired.
RaJi-cell growth was not affected. These results confirmed clinical
observations that T-cell functions were more sensitive to Cu
deprivation than B cells. Analysis of intracellular metal levels
in
Molt-3 cells showed that Cu levels had been significantly lowered
(P <
0.05) although Ca2+ levels were raised. Intracellular activity
of the
antioxidant enzyme superoxide dismutase (EC 1.15.1.1) was significantly
impaired (P < 0.05) in Molt-3 cells grown in Cu-depleted medium.
Activity of the mitochondrial enzyme cytochrome c oxidase (EC
1.9.3.1)
was also significantly impaired (P < 0.05) by Cu depletion.
Each of
these findings indicates an increase in the potential for cellular
damage by reduced antioxidant activity' impairment of normal
mitochondrial activity and excessive Ca2+ influx. A maJor consequence
of the type of damage occurring under these circumstances is
membrane
disruption. This was confirmed by scanning electron microscopy
of
Molt-3 cells grown under varying Cu levels. |
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