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Copper for iron absorption and utilization

Copper for iron absorption and utilization

Frequent Sickness. Med Copper for iron absorption and utilization Ansorption Exerc. In znd cross-sectional study in Heart health catechins women, of utilizaion had confirmed osteoporosis, lower serum copper concentrations abbsorption associated with osteoporosis in the Fat-free weight loss women tor years but not the older women ages years Background Deficiency of certain trace elements generally causes hypochromic microcytic anemia. Copper deficiency may cause iron deficiency anemia or compromise ATP production, resulting in weakness and fatigue. Copper dyshomeostasis in neurodegenerative diseases—therapeutic implications. Cells were washed and uptake was performed using 10 uM 55 Fe or 64 Cu for different times in transport buffer In mM: 50 MOPS-Na, 94 NaCl, 7.

Copper for iron absorption and utilization -

A venous blood sample was taken from each child and divided into three tubes. The first tube containing EDTA used for estimation of hematological parameters using Celttac autoanalyzer, these parameters included the red blood cell count RBC , hemoglobin Hb , hematocrit Hct , mean corpuscular volume MCV , mean corpuscular hemoglobin MCH , mean corpuscular hemoglobin concentration MCHC , and red cell distribution width RDW.

The second tube containing heparin for estimation of lead, copper and zinc by the atomic absorption spectrophotometer [ 16 ]. Perkin Elmer HGA Germany. The blood lead level BLL was determined by the graphite furnace atomic absorption spectrophotometer, where as Cu and Zn concentrations were measured with the flame atomic absorption spectrophotometer.

The third tube, Hitachi autoanalyzer was used for serum iron estimation using Roche reagent kits whereas Elecsys - Japan was used for estimating serum ferritin. Drinking water Samples were taken from tap and hand pump water for detection of lead level using the atomic absorption spectrophotometer Graphite Furnace, Perkin Elmer HGA, USA.

Lead level in piped water was found to be 2. Hand pump, water collected from two separate hand pumps in the rural area, revealed lead levels to be 3. Data was analyzed by SPSS Statistical Package for Social Sciences version Chi-square test was performed to compare individual characteristics and the t-test was performed to compare the hematological parameters between anemic and control groups.

Results were expressed as the mean ± standard deviation SD. A correlation was performed for the levels of lead, Fe, Cu and Zn in blood versus the different hematological parameters. This study was done on 60 children with ages ranging from 2 to14 years with a mean value of 6. Also, blood lead level was higher in males than females and those of low social standard.

In addition, it was higher in children of illiterate mothers and fathers, unemployed mothers and employed fathers. The difference in distribution was significant for the mild and severe form of anemia HBLL Comparison between mean values of different hematological parameters and serum ferritin in anemic and control groups were studied Table 4.

Regarding the hematological parameters, nearly all values were significantly lower among the anemic than the control group except for the RDW, which showed a highly significant elevation among the anemic group. As for the RBC count, no statistically significant difference was detected between the groups.

Whereas no statistically significant difference was seen between both groups for Cu and Zn levels Fig 1. Comparison between mean values of copper, zinc and iron levels in anemic and control groups. Table 5 reveals the correlation between the different hematological parameters and the blood levels of lead, Cu and Zn.

Assessment of mean values of iron Fe and ferritin among the low and high blood lead level groups revealed Table 6 significantly lower blood iron and ferritin levels in the high BLL group than those of the low BLL group More than half of the study children who also reported a significant association of moderate and severe anemia with However the current study is similar to the estimation obtained for children in India [ 17 , 18 ].

Schwartz et al [ 20 ]. In addition, Drossos et al [ 21 ]. Whereas on the contrary, Froom et al [ 22 ]. suggested that hemoglobin level did not correlate well with BLL and suggested that anemia is not related to lead at low BLL. However, other studies reported a variable association [ 23 — 27 ].

Lead causes anemia by impairing heme synthesis and increasing the rate of red blood cell destruction [ 28 ]. On the other hand, it is also possible that iron deficiency, which is a proven cause of anemia, leads to increase in the absorption of lead in the body, resulting in high BLL [ 29 , 30 ].

Although a causal pathway cannot be determined, yet the study findings clearly demonstrate an association between varying severity of anemia and elevated BLL.

Fe, Cu and Zn are essential elements for the maintenance of life and health. Pb which is a heavy metal, can be harmful to human health. Therefore, the blood level of these elements in children was determined.

Because of the presence of high BLL in drinking water, as reported by the WHO, this study was carried out to reveal the relationship between high blood lead levels, trace elements as well as hematological parameters in children. In the present study, the level of iron in the anemic group was found to be significantly lower than the control as was expected, similarly Jain et al [ 6 ].

represented measure finding. As Fe has an essential role in many biological processes and as deficiency is a World health problem, especially for infants and rapidly growing adolescents.

Therefore, it is important to maintain iron concentration within its narrow normal range [ 31 ]. In the present study serum Zn level of the anemic group is insignificantly lower than the control group.

There is an antagonism between Zn and Fe absorption from the gastrointestinal tract, as an increase iron concentration in the intestinal lumen may antagonize the uptake of Zn [ 32 ]. A study done by Sebahat et al [ 1 ]. found a decrease in serum Zn level and an increase in serum Cu level in the anemic group compared to the control group.

In accordance, although the present study revealed the Cu level to be higher in the anemic more than control group yet, this increase was not statistically significant. However, Cu has a role in the absorption of iron. The oxidation of ferrous iron into ferric state is carried by ceruloplasmin.

This depletion of Cu could impair iron absorption [ 33 ]. In the present study, the serum level of Pb in the anemic group was significantly higher than in the control. A possible explanation is that Fe deficiency increases absorption of Pb from the intestines.

Similarly a study carried out in Canada, revealed high BLL in babies with Fe deficiency [ 25 ]. Other studies revealed significant associations between Fe deficiency and high blood lead level [ 30 , 34 ]. The current results showed that Hb, Hct, MCV, MCH and ferritin values of children with anemia decreased and RDW level increased in comparison to control group.

Also, blood lead levels were higher in anemic children. This could be due to that decreasing iron level increases lead absorption that in turn affects heme synthesis, thus negatively affecting hematological parameters [ 28 ].

Moreover high BLLs were found to be associated with lower iron and ferritin levels than lower lead levels. This may be that iron absorption occurs predominantly in the duodenum and jejunum.

Also, a number of dietary factors influence iron absorption, where ascorbate and citrate increase its uptake. Lead in particular is a pernicious element to iron metabolism. As it is taken up by the iron absorption machinery instead of iron, and through competitive inhibition.

Further more, it interferes with a number of important iron dependent metabolic steps such as heme biosynthesis [ 2 ]. In investigated water samples were considered suitable for drinking according to the EMH [ 35 ]. In Dakahlya-Egypt, lead level in drinking water was higher than the permissible limit according to the WHO.

In Egypt, the control of lead is not efficient, so that the level of lead in drinking water in some sporadic areas is still high level [ 37 ]. In , tap water in Washington, DC, exceeded the Environmental Protection Agency EPA regulations.

This was because of a change in water disinfection procedures, which increased the water ability to leach lead from connector pipes between water mains and interior plumbing in old houses [ 38 ].

In developing countries such as India, control of lead pollution is much slower and more sporadic. The present work revealed an association between blood lead level and low serum iron and ferritin levels.

This is similar to several studies reporting higher proportions of children with elevated blood lead levels among those with low iron and ferritin levels [ 39 — 41 ]. These results suggest that inadequate iron status may amplify the effect of lead contamination in the environment by increasing absorption and possibly retention of lead in the body [ 39 ].

On the contrary Hershko et al [ 42 ], reported a lack of correlation between iron and blood lead in older children. High BLLs were associated with low blood level of iron and ferritin. Lead level in drinking water was high according to the WHO, and this may be one of the leading causes for elevating BLL in children.

Lead pollution might be controlled and steps should be taken to reduce the prevalence of childhood anemia. Sebahat T, Aziz P, Murat I, Gunfer T, Gulten E, Mevlut B, Yasin KT, Osman G: Interaction between anemia and blood levels of iron, zinc, copper, cadmium and lead in children.

Indian J Pediatr. Article Google Scholar. Goyer RA: Lead toxicity: current concerns. Environ Health Prespect. Article CAS Google Scholar. Ellis MR, Kane KY: Lightening the lead load in children.

Am Fam Physician. CAS PubMed Google Scholar. CDC: Preventing lead poisoning in young children: a statement by the Center for Disease Control and Prevention.

Atlanta, GA. pdf ]. Google Scholar. Abdel-Maaboud RM, El-Attar MM, Mohamad NA, Ahmed SA, Medhat A: Lead toxicity in some rural communities in Assiut Governorate. Ass Un Bull Environ Res. Jain NB, Laden F, Culler U, Shankar A, Kazani S, Garshick E: Relation between blood lead levels and childhood anemia in India.

Am J Epidemiol. Article PubMed Google Scholar. Lanphear BP, Matte TD, Rogers J: The contribution of lead contaminated house dust and residential soil to children's blood lead levels. A pooled analysis of 12 epidemiologic studies. Environ Res. CAS Google Scholar. Igwe JC, Abia AA: Equilibrium sorption isotherm studies of Cd II , Pb II and Zn II ions detoxification from waste water using unmodified and EDTA-modified maize husk.

Electronic J Biotechnology. Volesky B, Holan ZR: Biosorption of heavy metals. Foods that contain copper include oysters, liver, whole grain breads and cereals, shellfish, dark green leafy vegetables, dried legumes, nuts, and chocolate.

Anemia Taking copper supplements may help people who have anemia because of copper deficiency. Copper works together with iron to form red blood cells. Animal studies suggest that taking copper by mouth may help prevent and slow arthritis, but evidence in humans is lacking.

Copper bracelets are often marketed to people with both osteoarthritis and rheumatoid arthritis as a way to relieve symptoms, but there is no evidence that they work. There is some slight evidence that taking copper along with zinc, manganese, and calcium might help slow the rate of bone loss among postmenopausal women.

Multivitamins that include minerals usually have copper. Copper is also available as a separate oral supplement, and can be found as a topical gel, and in topical solutions.

The best way to get enough copper is through your diet. For your body to use copper, you need to have a balance of zinc and manganese.

The following lists provide the recommended daily dietary intake of copper for children and adults from the Food and Nutrition Board at the Institute of Medicine. If you take a copper supplement, you should also take a zinc supplement 8 to 15 mg of zinc for every 1 mg of copper , as an imbalance of these two minerals can cause other health problems.

Because of the potential for side effects and interactions with medications, you should take dietary supplements only under the supervision of a knowledgeable health care provider.

Too much copper can cause nausea, vomiting, stomach pain, headache, dizziness, weakness, diarrhea, and a metallic taste in the mouth. Copper toxicity is rare but can cause heart problems, jaundice, coma, even death. DO NOT use copper supplements if you have diarrhea.

If you have well water, you may want to get the water tested for mineral content. You can also get copper without knowing it from using copper cookware and from water coming through new copper pipes.

Avoid unlined copper cookware. Copper can leach out of pipes into water, especially hot water, if it sits in copper pipes for a long time.

Cook with cold water to avoid problems. Flushing the pipes by running cold water for 2 to 3 minutes can reduce copper. If you have blue-green stains around your faucet or sink, or if you detect a metallic taste to your water, you may want to have your water tested by a certified laboratory.

Children and people with Wilson disease which causes a build up of copper in the brain, liver, kidneys, and eyes , and people with hereditary conditions including idiopathic copper toxicosis and childhood cirrhosis, should not take copper supplements.

If you are being treated with any of the following medications, you should not use copper supplements without first talking to your health care provider. Birth control pills and estrogen following menopause: Birth control medications and estrogen replacement for post-menopausal women can increase blood levels of copper.

Nonsteroidal anti-inflammatory drugs NSAIDs : These pain relievers include aspirin, ibuprofen Advil, Motrin , and naproxen Aleve.

Copper binds to NSAIDs and may enhance their anti-inflammatory activity. Penicillamine: Penicillamine, a medication used to treat Wilson disease and rheumatoid arthritis, reduces copper levels.

Copper may lower the amount of penicillamine your body absorbs. Allopurinol Zyloprim : Test tube studies suggest that allopurinol, a medication used to treat gout, may reduce copper levels. Cimetidine Tagamet : Animal studies show that cimetidine, a medication used to treat ulcers and gastric esophageal reflux disease GERD , may raise copper levels in the body.

Nifedipine Procardia or Adalat : In a human study, people who took nifedipine had lower levels of copper in their red blood cells. Zinc: Several laboratory and human studies have found that taking high levels of zinc supplements over long periods of time may lower the body's ability to absorb copper.

The same does not seem to be true of eating foods that have copper. Ask your provider if you need zinc and copper supplementation. Araya M, Pizarro F, Olivares M, Arredondo M, Gonzalez M, Mendez M.

Understanding copper homeostasis in humans and copper effects on health. It becomes more common with age and has been linked to copper deficiency For example, an analysis of eight studies including over 2, people found that those with osteoporosis had lower levels of copper than healthy adults Copper is involved in processes that create cross-links inside your bones.

These cross-links ensure bones are healthy and strong 11 , 12 , Copper is involved in processes that help strengthen bone tissue.

Copper deficiency may promote osteoporosis, a condition of hollow and porous bones. Copper helps ensure optimal brain function and development.

Consequently, copper deficiency could cause problems with learning and memory. People with copper deficiency may find it harder to walk properly 19 , Enzymes use copper to maintain optimal health of the spinal cord.

Some enzymes help insulate the spinal cord, so signals can be relayed between the brain and body Copper deficiency may cause these enzymes to not work as effectively, resulting in less spinal cord insulation. This, in turn, causes signals to not be relayed as efficiently 21 , Walking is regulated by signals between the brain and body.

As these signals are affected, copper deficiency may cause loss of coordination and unsteadiness 19 , Copper is used by enzymes that help maintain a healthy nervous system, ensuring signals are sent efficiently to and from the brain. A deficiency can compromise or delay these signals, causing a loss of coordination or unsteadiness while walking.

Studies have shown that the T3 and T4 levels of thyroid hormones are closely linked to copper levels. When blood copper levels are low, these thyroid hormone levels fall. As a result, the thyroid gland may not work as effectively. Given that the thyroid gland helps regulate your metabolism and heat production, low thyroid hormone levels could make you feel colder more easily 26 , Copper helps ensure healthy thyroid hormone levels.

These hormones help regulate your metabolism and body heat. As a result, copper deficiency could make you feel cold. People with lighter skin usually have fewer, smaller and lighter melanin pigments than people with darker skin Interestingly, copper is used by enzymes that produce melanin.

Therefore, copper deficiency could affect the production of this pigment, causing pale skin 30 , However, more human-based research investigating the link between pale skin and copper deficiency is needed.

Copper is used by enzymes that make melanin, the pigment that determines skin color. Copper deficiency may cause pale skin. Given that low copper levels can affect melanin formation, copper deficiency may cause premature gray hair 32 , While there is some research on copper deficiency and melanin pigment formation, hardly any studies have looked at the link between copper deficiency and gray hair specifically.

More human-based research in this area would help clarify the link between the two. Like skin color, hair color is affected by melanin, which requires copper. This means copper deficiency may promote premature gray hair. Vision loss is a serious condition that may occur with long-term copper deficiency 34 , Copper is used by many enzymes that help ensure the nervous system works properly.

This means that copper deficiency can cause problems with the nervous system, including vision loss It seems that vision loss due to copper deficiency is more common among people who have had surgery on their digestive tract, such as gastric bypass surgery.

Inhibition of iron and copper uptake basorption iron, copper and Healthy metabolism catalyst. NÚÑEZ Fat-free weight lossMANUEL RUZ utilizatio and MANUEL OLIVARES 3. Department of Biology, Faculty of Sciences, and System Biology and Biotechnology Research Center, Universidad de Chile, and 3. Department of Nutrition, Faculty of Medicine, Universidad de Chile. Dirección para Correspondencia.

Copper for iron absorption and utilization -

Iscove's medium was purchased from GIBCO Life Technologies Carlsbad, CA. Fetal Bovine Serum FBS was from Clontech Palo Alto, CA. Medium was changed every two days. After seven days, cells were confluent 1. Caco-2 cells were incubated with Fe FeCl 3 · 6H 2 O as Fe-NTA 1: 2 , Cu CuSO 4 as Cu-histidine 1: 10 , and Zn ZnSO 4 · 7H 2 O as ZnCl 2.

Pre-treatment of Caco-2 cells with different extracellular metal concentrations. Cellular extracts were prepared from Caco-2 cells grown as described above. Cells were washed twice with PBS and then incubated with saline-Tris buffer in μM: 40 Tris-HCl, NaCl, pH 7.

The cell suspensions were transferred to a 1. The pellet was resuspended in 50 μL lysis buffer in mM: 10 Hepes pH 7. The supernatant was transferred to a 0. A 10 μL aliquot was taken for protein determination by using the Lowry method To determine Fe and Cu intracellular concentrations, Caco-2 cells were incubated at equilibrium with different concentrations of the single metals between 0 and μM for 7 days.

The cells were washed and a cellular extract was prepared. Cellular extract was digested with concentrated ultrapure nitric acid 1: 1 overnight at 60ºC. Fe and Cu content were determined by using an atomic absorption spectrometer AAS equipped with graphite furnace SIMAA , Perkin Elmer, Shelton, CT.

MR-CCHEN Venus antiqua and DOlt-2 Dogfish liver preparations were used as reference materials to validate the mineral analyses. To determine 55 Fe and 64 Cu uptake on Caco-2 cells incubated at equilibrium with different concentrations of metal, Caco-2 cells were incubated as described and supplemented with 5, 10, 20 and 50 uM of Fe, Cu or Zn for 7 days.

Cells were washed and uptake was performed using 10 uM 55 Fe or 64 Cu for different times in transport buffer In mM: 50 MOPS-Na, 94 NaCl, 7. Cells were washed and intracellular metal radioisotope and total concentration was measured in a Beta counter and by AAS. For competition studies, Caco-2 cells were grown for 7 days as above and then incubated in transport buffer with a 55 Fe: Zn, 55 Fe: Cu, 64 Cu: Fe or 64 Cu: Zn in varying ratios from 1: 0.

After the incubation, cells were washed and intercellular radioisotope was measured. Intracellular content of Fe, Cu and Zn in Caco-2 cells. Intracellular content of Fe, Cu and Zn in Caco-2 cells incubated with Fe or Cu are shown in figures 1A and 1B, respectively.

As expected, when extracellular Fe increased in the media 0. However, in the same conditions, both Cu and Zn decreased from 0. When Caco-2 cells were incubated with increasing Cu concentrations, intracellular Cu content increased from 0. In this situation, Fe decreased from 0.

Cells incubated in basal conditions, had a ratio of 1: 2: 4 of Fe: Cu: Zn, respectively. Effect of increasing intracellular concentrations of Fe, Cu or Zn over Fe or Cu uptake. To study the effect of the intracellular metal content on the uptake of Fe or Cu, Caco-2 cells were incubated with four concentrations 0.

Independently of the intracellular Cu or Zn concentrations Figs. However, Fe uptake in cells grown in different Cu concentrations was lower than in cells grown in different Zn concentrations.

In the same way, intracellular Fe or Zn concentrations Figs. Cu uptake in cells grown in different Zn concentrations was lower than in cells grown in different Fe concentrations. Studies of competition between metals Fe vs.

Cu or Zn and Cu vs. Fe or Zn. Fe at However, increased extracellular Zn concentrations did not affect Cu uptake Fig. Effect of different molar ratios over 55 Fe or 64 Cu uptake. Caco-2 cells were incubated with different molar ratios of 64 Cu: Fe: Zn or 55 Fe: Cu: Zn 1: 1: 1 a 1: 5; from 10 uM to 50 uM , and the uptake of Fe and Cu was studied.

Under these conditions, a ratio of 1: 1: 1 of 64 Cu: Fe: Zn Fig. Zn, Cu and Fe are essential mineral elements that exhibit important interactions and possible competitive inhibition of transport and bioavailability Reinstein et al. In this work, we studied the effects of iron, copper and zinc, alone or in combination in different metals ratios, on the absorption of each other.

In competition studies, we showed that Cu or Zn inhibited Fe uptake and Fe inhibited Cu uptake. However, Zn did not inhibit Cu uptake. When two metals were given together there was an evident inhibition in the uptake, especially over 1: 10 molar ratio.

Based on these results, a concern arises about the concentrations of minerals currently used in the programs of food fortification with multinutrients. These findings are especially relevant for the infantile milk formula field, since most of these preparations are fortified with copper, iron and zinc in molar ratios of 1: 5.

Future research is required to find the optimal molar ratios among these microminerals. Zn-Cu competition has been exploited beneficially for the treatment of Wilson's disease to avoid Cu accumulation Barone, Copper is a naturally occurring metal found in soil, water, and rocks.

Nutritionally, it is an essential trace mineral found in some foods and in supplements. It works to assist various enzymes that produce energy for the body, break down and absorb iron, and build red blood cells, collagen, connective tissue, and brain neurotransmitters. UL: The Tolerable Upper Intake Level UL is the maximum daily intake unlikely to cause harmful effects on health.

Because dozens of enzymes use copper to perform metabolic processes throughout the body, it is believed that both an excess and deficiency of copper may interrupt these normal processes and a stable level is required for optimal health.

The body is typically efficient at stabilizing copper levels absorption increases if copper intake is low, and vice versa. The muscles in the heart contain high concentrations of copper, and may be negatively affected by either a deficiency or toxicity of the mineral.

Copper may play a role in cancer for several reasons. It supports angiogenesis, the growth of blood vessels that feed a tumor, and activates enzymes and signaling proteins used by cancer cells.

Intentionally depleting copper levels by blocking its bioavailability may reduce the energy these cells need to travel in the body. Chelation-based treatments that bind to and inactivate copper are being researched. Copper is found in highest amounts in protein foods like organ meats, shellfish , fish , nuts , and seeds as well as whole grains and chocolate.

The absorption of copper in the body will increase if the diet contains less copper, and decrease if the body has enough copper.

A copper deficiency is rare in the U. A genetic condition called Menkes disease interferes with copper absorption, leading to severe deficiency that could become fatal without copper injections. Also, it is possible to create a copper deficiency by taking high doses of zinc supplements that can block the absorption of copper in the small intestine.

Toxicity is rare in healthy individuals as the body is efficient at excreting excess copper. Severe liver damage and digestive symptoms such as nausea, vomiting, diarrhea, and abdominal pain may occur. Immunohistochemistry Immunohistochemical detection of thiol adducts in mouse duodenum was performed using immunoperoxidase detection.

Western Blotting Isolated enterocytes were processed and protein fractions isolated as follows: proximal duodenum 2 cm was washed with ice cold PBS, cut vertically, placed in a 1. Statistical Analysis Data were analysed in Graphpad Prism 5 using 1-way or repeated measures ANOVA with Newman-Keuls posthoc testing.

Results Copper Deficiency Leads to Anemia in Mice To determine the extent to which copper deficiency affects duodenal iron homeostasis, an accepted nutritional paradigm of copper deprivation was used.

Download: PPT. Hypoxia Regulates Hif-2α Expression and Hif-2α-related Genes in the Duodenum of Copper Deficient Mice We next determined the effect of copper deficiency on the expression of iron-related molecules in the duodenum — iron transporters Dmt1 and Fpn and ferric reducatse Dcytb.

Figure 2. Iron absorption genes are regulated in copper deficiency. Figure 3. Copper deficiency anemia results in increases in duodenal hypoxia and Hif-2α but partial alleviation of anemia, by copper injection, reduces duodenal hypoxia and down regulates Hif-2α. Figure 4. Iron absorption genes are regulated in a HIF-2 dependent manner in copper deficiency.

Discussion The data presented demonstrate a new relationship between copper and iron homeostasis. This would involve at least 3 steps: Upregulation of FPN as a compensatory response to systemic copper deficit to adjust the rates of iron export.

This in turn is likely linked to decreased activity of the copper-dependent oxidases HEPH and CP. In support of this mechanism, Chen et al. have shown an increase in Slc40a1 mRNA levels in sex-linked anemia sla mice that carry an in-frame deletion in the Heph gene, resulting in partial loss of its activity and systemic iron deficiency [40] , [41].

In a agreement with our study increased duodenal Slc40a1 mRNA levels have also been reported in CuD mice [26].

Although we have not measured hephaestin activity directly it is likely to be significantly reduced. However other intestinal ferroxidases are known to be present in the gut, which could compensate, in part, for the loss of hephaestin and maintain some degree of iron efflux function [42] , [43].

Furthermore, Hamp1 levels in our copper-deficiency model were decreased, in agreement with a previous study [26]. Hamp1 levels were also not changed post copper injection although Fpn protein levels decreased, suggesting the latter to be a hepcidin independent event. Modulation of apical Dmt1 expression to regulate iron absorption.

However, severe copper deficiency in a number of animal studies has been shown to lead to iron retention in the gut due to impairment in basolateral iron export [26] , [44] — [46]. As such, high iron levels are expected to have a negative effect on Dmt1 expression.

This was in contrast to Fpn, Dcytb and Hif-2α which all increased Figure S2. Dcytb upregulation in copper deficiency to promote iron and copper absorption. Cybrd1 is one of a number of iron-related genes not to contain an IRE sequence.

Recent studies demonstrate that both Dcytb and the Steap proteins 2—4 are metalloreductases [2] , [3]. In the case of the Steap proteins, over-expression results in increased copper uptake.

More importantly however, in copper deficiency, we found Cybrd1 , but not the Steaps data not shown to be significantly upregulated in the duodenum.

It is tempting to envisage, depending on the context, Dcytb working in tandem with Ctr1 to enhance copper uptake.

Thus the role of Dcytb or Steaps in copper uptake in vivo warrants further analysis, for example using respective mouse knockout models. Figure 5.

Model for the role of HIF-2α in the adaptive response to copper deficiency anemia. Supporting Information. Figure S1. s TIFF. Figure S2. Figure S3.

Table S1. Primers sequences used for Real-time PCR. s EPS. Acknowledgments We thank Andrija Matak for assistance with hypoxyprobe immunohistochemistry, Jean-Christophe Deschemin Institut Cochin for experimental assistance and mouse management and Madeleine Flynn for graphical design QIMR.

Author Contributions Conceived and designed the experiments: PM SV CP. References 1. McKie AT, Barrow D, Latunde-Dada GO, Rolfs A, Sager G, et al. Science — View Article Google Scholar 2. Ohgami RS, Campagna DR, McDonald A, Fleming MD The Steap proteins are metalloreductases.

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BMC Research Notes utilizatikn 3Article aand Cite this article. Metrics Flavonoids and immune support. Anemia Fat-free weight loss absodption health problem among infants and children. It is often associated with a decrease in some trace elements iron, zinc, copper and an increase in heavy metals as lead. The study is a cross-sectional performed on 60 children. Copper for iron absorption and utilization

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6 Tell Tale Signs of a Copper Deficiency

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  1. Absolut ist mit Ihnen einverstanden. Darin ist etwas auch mir scheint es die gute Idee. Ich bin mit Ihnen einverstanden.

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