Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002871 (anemia)
 52,094 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Studies have been made on the effects of dietary copper on the iron and Cu distribution in rats and on the metabolic activity and absorptive capacity of intestines perfused both vascularly and luminally. 2. Rats maintained for 4-5 weeks on a Cu-deficient diet (0.4 microgram Cu/kg) had significantly lower plasma, liver and intestinal Cu concentrations and significantly reduced plasma caeruloplasmin and liver cytochrome c oxidase (EC 1.9.3.1) activity compared with controls receiving a Cu-supplemented diet (5 micrograms Cu/kg). Disturbances in Fe metabolism in Cu-deficient rats were evident as shown by a mild anaemia, significantly elevated hepatic Fe concentrations and hypoferraemia. 3. Intestinal glucose uptake from both the luminal perfusion medium (LPM) and vascular perfusion medium (VPM) was unaffected by Cu deficiency despite a significant (25-30%) reduction in oxygen consumption. This was associated with a 40% decline in mucosal cytochrome c oxidase activity. 4. In studies of Fe absorption, Fe uptake from the LPM was unaffected by Cu deficiency while transfer of Fe to VPM was significantly reduced (50%) compared with control preparations. Addition of apotransferrin (1 g/l) to the VPM was without effect in preparations from control rats but significantly increased the transfer of Fe to the VPM in preparations from Cu-deficient rats without affecting Fe uptake from the LPM. 5. The addition of either human or porcine caeruloplasmin (together with apotransferrin) to the VPM, such that the resultant ferroxidase (EC 1.16.3.1) activity of the VPM supernatant fraction was four to five times that of normal rat plasma, was without effect on either Fe uptake, tissue retention or Fe transfer to the VPM by preparations from either Cu-deficient or control rats. 6. These findings offer no evidence in support of the proposed role for caeruloplasmin with its associated ferroxidase activity in Fe absorption in the rat.
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PMID:Studies on the roles of apotransferrin and caeruloplasmin (EC 1.16.3.1) on iron absorption in copper-deficient rats using an isolated vascularly- and luminally-perfused intestinal preparation. 284 73

Experiments were conducted in suckling mice to investigate copper-dependent anemia. Brindled (Mobr/y) mice, which are not anemic, were compared to their normal brothers (Mo+/y) as well as to anemic suckling mice that were copper-deficient (-Cu) because their dams were consuming a diet low in copper and a fourth group of suckling mice that served as dietary controls (+Cu). Compared to +Cu and Mo+/y mice, -Cu mice were smaller and exhibited cardiac hypertrophy and significant atrophy of lymphoid tissues (spleen and thymus), Mobr/y mice were also small and demonstrated modest atrophy of both liver and spleen. Cu levels were decreased in all -Cu mouse tissues studied, whereas Fe levels tended to be unaltered. Mobr/y mice also exhibited lower tissue Cu levels in soft tissues, except for kidney and small intestine; however, Cu levels in Mobr/y mice were greater than in -Cu mice. Functional copper deficiency was demonstrated in -Cu tissues by decreases in cytochrome c oxidase (CO) and cuprozinc-superoxide dismutase (SOD). The magnitude of the change was tissue specific. Mobr/y tissues, which were low in Cu, also exhibited decreased SOD and CO activity. However, the drop in Mobr/y tissue was less than in -Cu tissue. This was most pronounced in bone marrow, where both CO and SOD were four times higher in Mobr/y than in -Cu mice. Both Mobr/y and -Cu mice had low serum ceruloplasmin activities. The presence of anemia in -Cu mice and the absence of anemia in Mobr/y mice may result from a more severe copper-deficient state in erythropoietic tissues in -Cu mice rather than from differences in ceruloplasmin activity.
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PMID:Changes in tissue growth, concentrations of copper, iron, cytochrome oxidase and superoxide dismutase subsequent to dietary or genetic copper deficiency in mice. 631

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.
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PMID:Copper deficiency alters isomyosin types and levels of laminin, fibronectin and cytochrome c oxidase subunits from rat hearts. 774 37

Trace mineral deficiencies tend to have profound effects on the integrity of formed blood elements. Anemia and neutropenia are commonly seen in copper (Cu) deficiency. We therefore developed a serum-free medium to examine the trace mineral requirements, in particular iron and Cu, for proliferation and retinoic acid (RA)-induced differentiation of HL-60 cells. This defined medium (DFM) was composed of Iscove's Modified Dulbecco's Medium (IMDM) supplemented with insulin and human apo-transferrin (each at 5 micrograms/ml) and 1.4 microM FeSO4. The iron concentration range for optimal cellular proliferation was narrow (2-3 microM). HL-60 cells could be maintained in DFM for 15 passages with a doubling time of 38-40 hr. The Cu content of IMDM was very low. Thus, by the fourth passage in DFM, the activity of cuproenzymes (cytochrome c oxidase, CCO; and copper-zinc superoxide dismutase, CuZnSOD) began to decline. Supplementation of DFM with CuSO4 (50 nM) restored enzyme activities. Treatment of cells with a Cu chelator (tetrathiomolybdate, 1 microM) rapidly reduced the activities of both CCO and CuZnSOD. Over the Cu concentration range examined (5-350 nM), Cu supplementation had little effect on HL-60 proliferation. Cell retained the ability to differentiate along the granulocytic pathway when treated with RA, but seemed to be less sensitive to the inducing agent except at the highest concentration tested (1 microM). This decreased sensitivity to RA did not seem to be related to the Cu status of the cells but rather to the absence of a component of serum. Indeed, cells grown in DFM regained their sensitivity to RA when allowed to differentiate in IMDM with 5% serum. These data indicate that the processes of growth and terminal differentiation in HL-60 cells are not greatly influenced by Cu. Thus, it seems likely that the insult resulting in neutropenia which is associated with Cu deficiency may occur earlier than the promyelocytic stage. However, the possibility that the mechanisms contributing to neutropenia may be unrelated to primary defects in the biochemistry of neutrophil maturation cannot be ruled out.
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PMID:Iron and copper requirements for proliferation and differentiation of a human promyelocytic leukemia cell line (HL-60). 777 91

To test the effect of food restriction on responses to dietary copper deficiency, male weanling rats were fed two amounts of dietary copper via five dietary-intake regimens ranging from ad libitum to 70% of ad libitum intake. Copper-deficient rats exhibited characteristic signs, including depressed organ copper content, reduced activity of copper-dependent enzymes, enlarged hearts, and anemia. Food restriction attenuated the cardiac enlargement, red blood cell defects, and reduction of superoxide dismutase activity in copper-deficient rats. Mineral and enzyme assays suggested that possible mechanisms for this amelioration are the correction of copper status and/or the improvement of antioxidant status. Also, food restriction depressed serum cholesterol and enhanced cytochrome c oxidase activity in both copper-adequate and copper-deficient rats, which compensated for effects of copper deficiency. A second experiment illustrated that the mortality associated with severe copper deficiency was also inhibited by food restriction.
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PMID:Amelioration of effects of severe dietary copper deficiency by food restriction in rats. 824 74

Deficiencies in the activity of cytochrome c oxidase (COX) are an important cause of autosomal recessive respiratory chain disorders. Patients with isolated COX deficiency are clinically and genetically heterogeneous, and mutations in several different assembly factors have been found to cause specific clinical phenotypes. Two of the most common clinical presentations, Leigh Syndrome and hypertrophic cardiomyopathy, have so far only been associated with mutations in SURF1 or SCO2 and COX15, respectively. Here we show that expression of COX10 from a retroviral vector complements the COX deficiency in a patient with anemia and Leigh Syndrome, and in a patient with anemia, sensorineural deafness and fatal infantile hypertrophic cardiomyopathy. A partial rescue was also obtained following microcell-mediated transfer of mouse chromosomes into patient fibroblasts. COX10 functions in the first step of the mitochondrial heme A biosynthetic pathway, catalyzing the conversion of protoheme (heme B) to heme O via the farnesylation of a vinyl group at position C2. Heme A content was reduced in mitochondria from patient muscle and fibroblasts in proportion to the reduction in COX enzyme activity and the amount of fully assembled enzyme. Mutation analysis of COX10 identified four different missense alleles, predicting amino acid substitutions at evolutionarily conserved residues. A topological model places these residues in regions of the protein shown to have important catalytic functions by mutation analysis of a prokaryotic ortholog. Mutations in COX10 have previously been reported in a single family with tubulopathy and leukodystrophy. This study shows that mutations in this gene can cause nearly the full range of clinical phenotypes associated with early onset isolated COX deficiency.
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PMID:Mutations in COX10 result in a defect in mitochondrial heme A biosynthesis and account for multiple, early-onset clinical phenotypes associated with isolated COX deficiency. 1292 84

Dietary nutrient interactions are important factors to consider in the study of nutrient status and requirements. Here, the effects of dietary interactions among copper (Cu), iron (Fe), manganese (Mn) and sulfur amino acids (SAA) on blood cell characteristics and enzyme activities were observed. Male rats (n = 8) were used in a 2 x 2 x 2 x 2 factorial design and fed an AIN-93G-based diet containing dietary Cu (<1 and 5 mg/kg), Fe (10 and 35 mg/kg), Mn (10 and 50 mg/kg) and either L-cystine (LCys) or DL-methionine (DLMet). Blood was analyzed by automated hematology cell counting and by flow cytometry. Severe Cu deficiency was verified by reductions in the activities of serum ceruloplasmin (1% of control), RBC superoxide dismutase (SOD1) (14% of control), liver cytochrome c oxidase activity (25% of control) and serum extracellular SOD (SOD3) activity (20% of controls). Because Cu is required for Fe utilization, many physiologic responses that require Fe were affected by both deficiencies, including lowered blood hemoglobin (Hgb), lower RBC volume and Hgb concentration, and an increased number of reticulocytes. Cu and Fe deficiencies together worsened some conditions, i.e., lower Hgb, lower RBC Hgb, increased RBC distribution width, increased number of reticulocytes and nucleated RBC, and a higher platelet count. Increasing dietary Mn had little effect on most variables, except to reduce serum Cu when dietary Cu was adequate but not when it was low, and to reduce RBC SOD1 activity when dietary Fe was low but not when it was adequate. Hgb concentrations were higher (P < 0.002) in Cu-deficient rats fed LCys than in those fed DLMet. There was no effect in Cu-adequate rats. Hgb was higher (P < 0.004) in Fe-adequate rats fed LCys than in those fed DLMet, with no effect in Fe-deficient rats. Although the anemia of Cu deficiency in AIN-93G-fed rats was not as pronounced as that reported in rats fed the AIN-76A-based diet, other manifestations of the deficiency were prominent.
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PMID:Contrasting and cooperative effects of copper and iron deficiencies in male rats fed different concentrations of manganese and different sources of sulfur amino acids in an AIN-93G-based diet. 1474 82

The morphology of gastrocnemius muscles was examined in RFPs (renal failure patients) being treated using HD (haemodialysis) and CAPD (continuous ambulatory peritoneal dialysis). RFPs (n=24) volunteered to participate in the present study. Twelve RFPs (five women and seven men; mean age, 55 years) were undergoing CAPD treatment and 12 RFPs (two women and ten men; mean age, 62 years) were undergoing HD treatment. Muscle biopsies from gastrocnemius muscles were found not to differ (P>0.05) in fibre type distribution, MyHC (myosin heavy chain) expression or fibre CSA (cross-sectional area) between the two groups. There were, however, significant differences (P<0.05) in CC/F (capillary contact/fibre), C/F (capillary to fibre ratio) and cytochrome c oxidase activity. The HD group had 33% more CC/F, with a 19% higher C/F and 33% greater cytochrome c activity in glycolytic fibres (II) than the CAPD group. There were no apparent differences in age, gender, co-morbidity, self-reported physical activity or physical functioning between the two groups, which could account for the difference in muscle capillarity between the groups. The HD patients were, however, administered heparin as a routine part of the dialysis therapy. The possibility is discussed that heparin in combination with mild anaemia and acidosis may have augmented angiogenesis in the HD patients.
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PMID:Skeletal muscle morphology and capillarization of renal failure patients receiving different dialysis therapies. 1525 90

Klotho, an antiaging gene with restricted organ distribution, is mainly expressed in the kidney tubules; the mutant mice have shortened life span, arteriosclerosis, anemia, and osteoporesis, features common to patients with chronic renal failure. Conceivably, the reduction of the Klotho gene expression may contribute to the development of kidney failure; alternatively, its overexpression may lead to the amelioration of renal injury in an ICR-derived glomerulonephritis (ICGN) mouse model with subtle immune complex-mediated disease. To address this issue, four different strains of mice were generated by cross-breeding: ICGN mice without the Klotho transgene (ICGN), ICGN mice with the Klotho transgene (ICGN/klTG), wild-type mice with the Klotho transgene (klTG), and wild-type mice without the Klotho transgene (control). At 40 weeks old, the survival rate was approximately 30% in ICGN mice, and approximately 70% in the ICGN/klTG group. This improvement was associated with dramatic improvement in renal functions, morphological lesions, and cytochrome c oxidase activity but a reduction in beta-galactosidase activity (a senescence-associated protein), mitochondrial DNA fragmentation, superoxide anion generation, lipid peroxidation, and Bax protein expression and apoptosis. Interestingly, improvement was seen in both the tubular and glomerular compartments of the kidney, although Klotho is exclusively confined to the tubules, suggesting that its gene product has a remarkable renoprotective effect by potentially serving as a circulating hormone while mitigating the mitochondrial oxidative stress.
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PMID:Amelioration of progressive renal injury by genetic manipulation of Klotho gene. 1728 45

Copper (Cu) deficiency during perinatal development in rats is associated with anemia, lower plasma iron (Fe), and brain Fe. Experiments were conducted to inject Fe dextran into Cu-deficient (Cu-) rat pups to attempt to reverse these conditions. Previous work with older Cu- rats did not reverse anemia following Fe injection. Dams began Cu-adequate (Cu+) or Cu- dietary treatments starting at embryonic d 7 and lasting through weaning. In Expt. 1, pups from each dietary treatment were given a single dose of Fe, 20 mg Fe/kg, or saline (S) at postnatal d 11 (P11). Plasma Fe and hemoglobin were higher in the Fe-injected groups at P13. Brain Fe deficit and brain transferrin receptor enhancement were eliminated in the Cu- group injected with Fe compared with Cu-S pups, supporting an association between low plasma Fe and low brain Fe. In Expt. 2, Fe treatment was increased to 45 mg Fe/kg. Four injections were given between P5 and P18 (total dose, 5-7 mg Fe). At P20, Fe concentrations in 4 brain regions (cortex, cerebellum, medulla/pons, and hypothalamus) generally were higher in all groups than in Cu-S pups. At P25, impaired vibrissae-elicited foot placement was evident in Cu-S rats and was not improved by Fe injection. However, at P26, the brain Fe deficit in Cu-S pups was eliminated by Fe injection. Fe injections in Cu- pups raised plasma Fe, brain Fe, and hemoglobin but did not reverse low cytochrome c oxidase or abnormal striatal behavior.
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PMID:Iron injection restores brain iron and hemoglobin deficits in perinatal copper-deficient rats. 1880 96


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