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Title
Two copper-responsive elements associated with the Chlamydomonas
Cyc6 gene function as targets for transcriptional activators.
Author
Quinn JM; Merchant S
Address
Department of Chemistry and Biochemistry' University of California
at
Los Angeles 90095-1569' USA.
Source
Plant Cell, 7(5):623-8 1995 May
Abstract
In Chlamydomonas reinhardtii' cytochrome c6 (cyt c6) is synthesized
only under conditions of copper deficiency when plastocyanin
cannot be synthesized. In previous work' the copper-responsive
regulation of cyt c6 synthesis was demonstrated to occur by control
of transcription' with no contribution from post-transcriptional
processes. To understand the mechanism underlying its regulation'
the genomic DNA encoding cyt c6 (Cyc6) was analyzed for the presence
of copper-responsive elements. Sequences lying between positions
-127 and -7 with respect to the start site of transcription were
found to be sufficient to confer copper-responsive expression
on either a promoterless or a minimal beta-tubulin promoter-driven
(arylsulfatase-encoding) reporter gene. Analysis of this 120-bp
fragment indicated that copper-responsive elements lie in two
distinct regions (between -110 to -56 and -127 to -109). ATG
fusions between copper-insensitive promoters and the coding plus
3` untranslated region of the Cyc6 gene resulted in the accumulation
of cyt c6 in copper-supplemented medium; this confirms earlier
studies indicating a lack of post-transcriptional control in
this copper-responsive pathway. In the context of a constitutive
promoter (derived from the beta-tubulin gene)' each region was
found to function as an activator of transcription in copper-deficient
cells' and the metal specificity of the response of reporter
genes containing either one or both regions was identical to
that of the endogenous Cyc6 gene. The copper-responsive synthesis
of cyt c6 is thus attributed to these two 5` upstream sequences.
Title
Nutrient intake of patients with rheumatoid arthritis is deficient
in
pyridoxine' zinc' copper' and magnesium.
Author
Kremer JM; Bigaouette J
Address
Department of Medicine' Albany Medical College' NY 12203' USA.
Source
J Rheumatol, 23(6):990-4 1996 Jun
Abstract
OBJECTIVE: To determine nutrient intake of patients with active
rheumatoid arthritis and compare it with the typical American
diet (TAD) and the recommended dietary allowance (RDA). METHODS:
41 patients with active RA recorded a detailed dietary history.
Information collected was analyzed for nutrient intake of energy'
fats' protein' carbohydrate' vitamins and minerals' which were
then statistically compared with the TAD and the RDA. RESULTS:
Both men and women ingested significantly less energy from carbohydrates
[women 47.4% (6.4) vs 55% RDA. p = 0.0001: men = 48.9% (7.4).
p = 0.025 and more energy from fat [women = 36.8% (4.5) vs 30%
RDA. p = 0.001 and men = 35.2% (5.9) p = 0.02 . Women ingested
significantly more saturated and mono-unsaturated fat than the
RDA (p = 0.02 and p = 0.04 respectively) while men ingested significantly
less polyunsaturated fat (PUFA) (p = 0.0001). Both groups took
in less fiber (p = 0.0001). Deficient dietary intake of pyridoxine
was observed vs the RDA for both sexes (men and women p = 0.0001).
Deficient folate intake was seen vs the TAD for men (p = 0.02)
with a deficient trend in women (p = 0.06). Zinc and magnesium
intake was deficient vs the RDA in both sexes (p values <
or = 0.001) and copper was deficient vs the TAD in both sexes
(p = 0.004 women and p = 0.02 men). CONCLUSION: Patients with
RA ingest too much total fat and too little PUFA and fiber. Their
diets are deficient in pyridoxine' zinc and magnesium vs the
RDA and copper and folate vs the TAD. These observations' also
documented in previous studies' suggest that routine dietary
supplementation with multivitamins and trace elements is appropriate
in this population.
Title
Requirements and toxicity of essential trace elements' illustrated
by zinc and copper.
Author
Sandstead HH
Address
Department of Preventive Medicine and Community Health' University
of Texas Medical Branch' Galveston 77555-1109.
Source
Am J Clin Nutr, 61(3 Suppl):621S-624S 1995 Mar
Abstract
Early signs of toxicity of essential trace elements are important.
Some trace elements are available over-the-counter (OTC) and/or
are present at industrial waste sites. Physicochemically similar
trace elements compete for ligands' impairing functions' which
is exemplified by the zinc-copper antagonism described long ago
by Van Campen' Hill and Matrone' and Klevay. Intestinal absorption
of copper is inhibited by zinc. Thus risk of copper deficiency
is increased when the molar ratio of zinc to copper (Zn:Cu) is
high. As shown by experiments' copper deficiency can occur in
humans. Manifestations include decreased erythrocyte copper-zinc
superoxide dismutase' increased low-density-lipoprotein cholesterol'
decreased high-density-lipoprotein cholesterol' decreased glucose
clearance' decreased methionine and leucine enkephalins' and
abnormal cardiac function. Calculation of a preliminary reference
dose for OTC zinc that assumed high bioavailability and uncertain
copper intakes established 9 mg as a safe amount for 60-kg adults.
Title
Effects of dietary copper deficiency on relative food intake
and growth efficiency in rats.
Author
Allen CB
Address
Department of Nutrition' University of California' Davis 95616-8669'
USA. challen@ucdavis.edu
Source
Physiol Behav, 59(2):247-53 1996 Feb
Abstract
Weanling male rats were fed either copper-adequate (CuA) or copper-deficient
(CuD) diets ad lib for 20 wk. A pair-fed group was also studied.
Two relative food intake indices (RFIs) and a growth efficiency
(GE) index were calculated. Body weights of the CuD group became
reduced compared to the CuA group starting the sixth week of
the study. copper deficiency was found to affect both of the
RFI indices and the GE index in a time-dependent manner. RFIs
and GE were reduced early' but recovered towards the control
values during the last half of the experimental period. At the
end of 20 wk' organ copper content and serum ceruloplasmin was
reduced in the CuD group. Dietary copper deficiency reduces growth
rate through effects both on food intake and efficiency of food
utilization for growth.
Title
Newer findings on a unified perspective of copper restriction
and cardiomyopathy.
Author
Medeiros DM; Wildman RE
Address
Department of Human Nutrition and Food Management' Ohio State
University' Columbus 43210-1295' USA.
Source
Proc Soc Exp Biol Med, 215(4):299-313 1997 Sep
Abstract
The cuproenzymes lysyl oxidase' cytochrome-c oxidase' and superoxide
dismutase are key factors in understanding the cardiac hypertrophy
and cardiomyopathy associated with dietary copper restriction.
The role of copper in cardiac lipid and energy metabolism as
a consequence of changes in some of these enzyme activities in
comparison with what is known about normal cardiac substrate
utilization is discussed here. While the decrease in the nuclear
encoded subunits of cytochrome-c oxidase in hearts from copper-deficient
rats is known' new evidence suggests that other factors' such
as ATP synthase metabolism may be exerting an influence upon
this observation. While this review focuses on newer knowledge
about energy and fatty acid metabolism in copper deficiency'
the extracellular matrix is considered as well. This complex
interplay of extracellular and cellular events in copper restriction
is outlined as a model for further studies of this unique model
of concentric hypertrophy.
Title
Effects of copper deficiency and copper deficiency coupled with
high dietary iron or molybdenum on phagocytic cell function and
response of calves to a respiratory disease challenge.
Author
Gengelbach GP; Ward JD; Spears JW; Brown TT Jr
Address
Department of Animal Science' North Carolina State University'
Raleigh 27695' USA.
Source
J Anim Sci, 75(4):1112-8 1997 Apr
Abstract
A study was conducted to determine the effects of supplementing
a diet marginally deficient in copper (Cu) with iron (Fe)' molybdenum
(Mo)' or Cu on phagocytic cell function and disease resistance
of calves. Thirty-one calves were born to heifers fed a corn
silage-based diet containing 4.5 mg of Cu/kg. Treatments consisted
of 1) control (CON; no supplemental Cu' Fe' or Mo)' 2) 600 mg
of Fe added/kg (FE)' 3) 5 mg of Mo added/kg (MO)' or 4) 10 mg
of Cu added/kg of DM (CU). Activity of superoxide dismutase was
lower (P < .06) in neutrophils from MO vs CON or CU calves
at 170 d of age. bactericidal activity of neutrophils from MO
calves tended (P = .15) to be lower compared with those from
CU calves at 70 d of age. Calves were inoculated intranasally
with live infectious bovine rhinotracheitis virus (IBRV) 2 d
after weaning' followed by intratracheal administration of Pasteurella
hemolytica 5 d later. Iron- and Cu-supplemented calves exhibited
higher (P < .01) body temperatures and lower (P < .06)
feed intakes following IBRV inoculation compared with CON and
MO calves. copper-supplemented calves had higher levels of plasma
tumor necrosis factor (TNF) than MO calves at weaning (P <
.05) and tended to have higher plasma TNF (P = .11) than FE and
MO calves 5 d after IBRV inoculation. These data indicate that
dietary levels of Mo and Cu can affect body temperature and feed
intake responses to disease by affecting TNF and perhaps other
cytokines.
Title
Hemostatic mechanisms in marginally copper-deficient rats.
Author
Schuschke LA; Saari JT; Miller FN; Schuschke DA
Address
Department of Pediatrics' University of Louisville' KY 40292'
USA.
Source
J Lab Clin Med, 125(6):748-53 1995 Jun
Abstract
Severe dietary copper restriction has been shown to alter platelet
structure and function and to significantly delay thrombogenesis
and hemostasis in rats. In the present study' the relationship
between dietary copper status and hemostasis were determined
in the rat cremaster muscle microcirculation. Male' weanling
Sprague-Dawley rats were fed a purified diet that was made copper-adequate
by addition of 6.0 micrograms copper/gm of diet (CuA) or was
marginally deficient by adding 1.5 micrograms (CuM1.5) or 3.0
micrograms (CuM3.0) copper/gm of diet for 1' 3' or 5 weeks. The
rats were anesthetized with sodium pentobarbital' and the cremaster
was spread in a Krebs`-filled tissue bath. Hemostasis was quantified
after two methods of thrombus induction: (1) micropuncture of
a 60 to 80 microns venule' which exposes subendothelial structures'
and (2) intravascular light-dye photochemistry' which does not
expose the subendothelial collagen. The CuM1.5 and CuM3.0 diets
significantly decreased hepatic copper after 3 weeks as compared
with the CuA diet. Bleeding time after micropuncture was significantly
longer at all times in the CuM1.5 group and after 5 weeks in
the CuM3.0 group. Platelet thrombus formation and time to vessel
occlusion in the light dye-treated vessels were not different
between any of the dietary groups at any times tested. There
was also no difference in prothrombin time (PT)' in the activity
of copper-related plasma coagulation factors V and VIII' or in
the hematocrit between the CuA and CuM1.5 groups.(Abstract TRUNCATED
AT 250 WORDS)
Title
copper biochemistry and molecular biology.
Author
Linder MC; Hazegh-Azam M
Address
Department of Chemistry and Biochemistry' California State University'
Fullerton 92634' USA.
Source
Am J Clin Nutr, 63(5):797S-811S 1996 May
Abstract
In this review' our basic and most recent understanding of copper
biochemistry and molecular biology for mammals (including humans)
is described. Information is provided on the nutritional biochemistry
of copper' including food sources' intestinal absorption' transport'
tissue distribution' and excretion' along with descriptions of
copper binding proteins and other factors involved and their
roles in these processes. The metabolism of copper and its importance
for the functions of a roster of vital enzymes is detailed. Its
potential toxicology is also addressed. Alterations in copper
metabolism associated with genetic and nongenetic diseases are
summarized' including potential connections to inflammation'
cancer' atherosclerosis' and anemia' and the effects of genetic
copper deficiency (Menkes syndrome) and copper overload (Wilson
disease). Understanding these diseases suggests new ways of viewing
the normal functions of copper and provides new insights into
the details of copper transport and distribution in mammals.
Title
copper supplementation of adult men: effects on blood copper
enzyme activities and indicators of cardiovascular disease risk.
Author
Jones AA; DiSilvestro RA; Coleman M; Wagner TL
Address
Department of Human Nutrition and Food Management, Ohio State
University, Columbus 43210-1295, USA.
Source
Metabolism, 46(12):1380-3 1997 Dec
Abstract
In rats, copper deficiency leads to low copper metalloenzyme
activity, high serum cholesterol, and cardiovascular lesions.
In humans, moderately low copper intake may be common, but the
consequences remain largely uncertain. The present study examined
the effects of copper supplementation (2 mg/d for 4 weeks in
a copper/placebo crossover design) in 20 adult men with moderately
high plasma cholesterol. End-point measurements were three copper
enzyme activities, erythrocyte superoxide dismutase (SOD), plasma
ceruloplasmin (Cp), and plasma diamine oxidase (DAO), and three
parameters related to the risk of cardiovascular disease (CVD),
plasma cholesterol, plasma lipoprotein (a) [Lp(a) , and lag times
for very-low-density lipoprotein (VLDL) and low-density lipoprotein
(LDL) oxidation in vitro. Although copper had no significant
effects on any parameter for the entire study group, it did significantly
increase two enzyme activities (SOD and DAO), as well as lipoprotein
oxidation lag times, in 10 subjects in the lower half of a median
split for precopper values. Thus, copper supplementation appeared
to influence some types of measurements in subjects beginning
with less than median values.
Title
Dietary copper in excess of nutritional requirement reduces plasma
and breast muscle cholesterol of chickens.
Author
Bakalli RI; Pesti GM; Ragland WL; KonJufca V
Address
Department of Poultry Science' University of Georgia' Athens
30602-2772' USA.
Source
Poult Sci, 74(2):360-5 1995 Feb
Abstract
Male commercial broiler strain chickens were fed from hatching
to 42 d of age either a control diet (based on corn and soybean
meal) or the control diet supplemented with 250 mg copper/kg
diet from cupric sulfate pentahydrate (for 35 or 42 d). Hypocholesterolemia
(11.8% reduction) and decreased breast muscle cholesterol (20.4%
reduction) were observed in copper-supplemented birds. There
was a slight increase (P > .05) in breast muscle copper (14.5%)'
and all levels were very low (< .5 mg/kg). Feeding copper
for 42 vs 35 d resulted in lower levels of cholesterol in the
plasma (12.9 vs 10.8% reduction) and breast muscle (24.6 vs 16.2%
reduction). Very similar results were found in two additional
experiments in which hypocholesterolemia and reduced breast muscle
cholesterol were associated with reduced plasma triglycerides
and blood reduced glutathione. It is well known that hypercholesterolemia
is a symptom of dietary copper deficiency. The data presented
here indicate that blood and breast muscle cholesterol are inversely
related to dietary copper in excess of the dietary requirement
for maximal growth. The cholesterol content of the edible muscle
tissue of broiler chickens can be reduced by approximately 25%
after feeding a supranormal level of copper for 42 d without
altering the growth of the chickens or substantially increasing
the copper content of the edible meat.
Title
Decreased carbonic anhydrase III levels in the liver of the mouse
mutant `toxic milk` (tx) due to copper accumulation.
Author
Grimes A; Paynter J; Walker ID; Bhave M; Mercer JF
Address
Scobie and Claire Mackinnon Trace Element Group' Royal Children`s
Hospital' Parkville' Victoria' Australia.
Source
Biochem J, 321 ( Pt 2)():341-6 1997 Jan 15
Abstract
The mouse mutant `toxic milk` (tx) is characterized by marked
hepatic accumulation of copper' similar to that found in patients
with the genetic disorder of copper transport' Wilson disease.
In addition' lactating tx females produce copper-deficient milk.
To characterize further the biochemical basis of this defect'
Western blots of tissue extracts from normal and tx mice were
probed with various heavy-metal radioisotopes (63Ni. 65Zn and
64Cu). A 30 kDa Ni/Zn-binding polypeptide was found to be markedly
decreased in the livers of the tx mice. This protein was isolated
from normal adult mice using a procedure based on Ni-chelation
chromatography. The amino acid sequences of two CNBr peptides
were identical with portions of the mouse skeletal muscle carbonic
anhydrase III (CAIII) sequence. Two other peptides sequenced
had closely related sequences to that of CAIII' but with two
differences in 45 amino acids. These two peptides may be derived
from a novel CAIII isoform' which we term CAIIIB to distinguish
it from the published form' CAIIIA. We isolated a cDNA clone
corresponding to CAIIIA and used this to show that CAIIIA mRNA
was also decreased in the mutant liver' but not in muscle. copper
loading of normal mice also decreased hepatic CAIIIA mRNA' suggesting
that the decrease in CAIII mRNA in the tx mouse liver is a secondary
consequence of the high copper levels in the liver.
Title
The effect of molybdenum-induced copper deficiency on acute-phase
protein concentrations' superoxide dismutase activity' leukocyte
numbers' and lymphocyte proliferation in beef heifers inoculated
with bovine herpesvirus-1.
Author
Arthington JD; Corah LR; Blecha F
Address
Departments of Animal Sciences and Industry' Kansas State University'
Manhattan 66506-0201' USA.
Source
J Anim Sci, 74(1):211-7 1996 Jan
Abstract
This study was conducted to determine the effect of Cu deficiency
on acute-phase protein concentrations' superoxide dismutase activity'
leukocyte numbers' and lymphocyte proliferation in heifers inoculated
with live bovine herpesvirus-1 (BHV-1). Hereford x Angus heifers
were allotted by weight and initial liver Cu concentrations into
molybdenum (Mo)-supplemented (n = 6) or control (n = 6) groups.
Control heifers were fed a basal diet supplemented with Cu-sulfate
to achieve a dietary concentration of 8 ppm of Cu. The Mo-supplemented
heifers received the basal diet supplemented with Mo to achieve
a dietary Mo:Cu ratio of 2.5:1 and with sulfur at .3% of the
diet. All treatments were delivered for 129 d' when heifers were
inoculated intranasally with BHV-1. To ensure adequate Cu stores
before viral challenge' control heifers were given a cupric glycinate
inJection on d 100 of treatment. On d 129' Mo-supplemented heifers
were considered Cu-deficient (liver Cu = 23.2 and 90.1 ppm for
Mo-supplemented and control' respectively). Neutrophils were
increased (P < .01) on d 129 in Mo-supplemented heifers. Ceruloplasmin'
a copper-dependent acute-phase protein' increased (P < .01)
by 48 h after challenge in control but not in Mo-supplemented
heifers. Fibrinogen' an acute-phase protein not containing copper'
increased by 48 h after challenge in Mo-supplemented but not
in control heifers. Erythrocyte superoxide dismutase (SOD) activity
was less (P < .05) in Mo-supplemented heifers on d 129. Viral
challenge had no effect on SOD activity. Lymphocyte proliferative
response to phytohemagglutinin stimulation was greater (P <
.01) for Mo-supplemented heifers following BHV-1 challenge. No
differences were detected when lymphocytes were stimulated with
concanavalin-A or pokeweed mitogens. These data indicate that
Cu deficiency alters the acute-phase protein response to viral
infection and may affect lymphocyte responsiveness to mitogen
stimulation.
Title
Suspected nutritional deficiency causing anaemia in llamas (Lama
glama).
Author
Andrews AH; Cox A
Address
Department of Farm Animal and Equine Medicine and Surgery' Royal
Veterinary College' North Mymms' Hatfield.
Source
Vet Rec, 140(6):153-4 1997 Feb 8
Abstract
A case of poor condition and recumbency in a 14-month-old female
llama and a case of poor condition and ataxia in a 23-month-old
male llama are described. Both animals were anaemic and had low
plasma copper levels. An increased intake of feed with a higher
copper level and treatment with copper inJections and an oral
mineral solution resulted in a successful recovery. Two other
young llamas also had low plasma copper levels. The problem was
probably due to a nutritional' particularly copper' deficiency
and the animals recovered as their copper levels increased. |
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