Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P02794 (ferritin)
 17,525 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The assessment of the iron (Fe) status is very important because its deficiency is one of the most common in both developing and industrialized countries, being particularly prevalent among infants and young children. Diagnosis is difficult in the presence of other conditions which interfere with the interpretation of laboratory tests, such as hemoglobin (Hb), hematocrit (Hct), serum iron, transferrin saturation percentage and serum ferritin. Free erythrocyte protoporphyrin (FEP) is a precursor of Heme and normally occurs in very low concentration in red blood cells (RBC); elevated values indicate early impaired iron nutritional status, providing information about gradual changes in the iron supply to the marrow. This laboratory test is a practical and convenient method because it needs a small blood sample easily preserved. Although the Second National Health and Nutritional Examination Survey (NHANES II) of USA has provided a good opportunity to define more precisely the cut-off points, it is doubtful whether the age-related differences in children represent normal development or the effects of iron deficiency. In order to provide information about these aspects the present experimental model was performed: weanling Wistar rats were fed until 95 days of age (t 95) with an isocaloric diet containing 20 or 30 g/100 g. of protein (casein) (N 20 and N 30, respectively), allowing the highest growth and erythropoiesis rates and covering the requirements of all the nutrients (Table 1). Body weight and food intake were recorded three times/week.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Free erythrocyte protoporphyrin as a function of age in growing rats]. 824 30

Heme oxygenase-1 mRNA levels increase following exposure of many mammalian cell lines to oxidative stress such as ultraviolet A (UVA) irradiation. Here we demonstrate a 4-fold increase in microsomal heme oxygenase activity and a 40% decrease in microsomal heme content 14 h after treatment of human skin fibroblasts (FEK4) with 250 kJ m-2 of UVA radiation. Paralleling this was a 2-fold increase in ferritin levels that was sustained for at least 46 h after UVA irradiation. Treatment of fibroblasts with the iron chelating agent desferrioxamine, after the UVA-dependent induction of heme oxygenase, prevented the increase in ferritin levels. Treatment of fibroblasts with Sn-protoporphyrin IX (an inhibitor of heme oxygenase) also prevented the effect of UVA radiation on ferritin levels. Thus we conclude that the effect of UVA radiation on ferritin levels is via the heme oxygenase-dependent release of iron from endogenous heme sources. We propose that the increase in ferritin that follows UVA irradiation would decrease intracellular free iron such that iron-catalyzed free radical reactions would be restricted during periods of subsequent oxidative stress.
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PMID:Oxidative stress resulting from ultraviolet A irradiation of human skin fibroblasts leads to a heme oxygenase-dependent increase in ferritin. 832 45

The Chilean School Lunch program, which serves one million children nationwide, was supplied with three 10-g cookies fortified with 6% bovine hemoglobin concentrate, designed to provide 1 mg bioavailable iron per day. A survey of 1000 children was performed after 3 y. Significant differences in hemoglobin concentrations were found in the children from the fortified vs the nonfortified province (P < 0.01). Low serum ferritin values were also significantly more prevalent in the nonfortified group. The effect was evident despite the very low prevalence of anemia in both the fortified and the unfortified school groups. Heme-iron-fortified cookies are a feasible and effective way to improve the iron status of school-age children. In regions of high prevalence of iron-deficiency anemia, the effect of a heme-fortified cookie program should be even more important.
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PMID:Effect of bovine-hemoglobin-fortified cookies on iron status of schoolchildren: a nationwide program in Chile. 842 87

Heme oxygenase (HO) is the rate-limiting enzyme in the catabolism of heme to bilirubin. Cobalt chloride (CoCl2) and many other agents that generate oxidant stresses induce the HO-1 isoform. Furthermore, HO-1 has been shown to protect against oxidant stress in vitro and in vivo by mechanisms involving increased ferritin synthesis. However, little is known about the inducibility of hepatic HO-1 during the very early postnatal period, and whether HO-1 induction is associated with increased ferritin synthesis in neonates. Therefore, we studied hepatic HO-1 mRNA, HO-1 protein concentration, total HO activity, and ferritin protein levels in neonatal rats. Neonatal rats 0-5 d of age were injected with 250 mumol/kg body weight of CoCl2. 6H2O in saline or with an equal volume of saline in age-matched controls. Liver samples were collected 4 h after injection for HO-1 mRNA analysis and 20 h after injection for analysis of HO-1 protein concentration, total HO activity, and ferritin protein levels. In CoCl2-treated rats, hepatic HO-1 mRNA was 3-10 times the levels in control rats (p < 0.05), HO-1 protein concentration was 2-5 times the levels in control rats (p < 0.05), and total HO activity was higher by 20-80% than in control rats (p < 0.05). There were no differences in hepatic ferritin protein levels between CoCl2-treated neonatal rats and controls; however, in CoCl2-treated adult rats, hepatic ferritin protein levels were 1.6 times the levels in controls (p < 0.05). Thus, neonatal rats can up-regulate hepatic HO-1 mRNA, HO-1 protein concentration, and total HO activity in response to CoCl2; however, no upregulation of hepatic ferritin protein levels was observed in neonatal rats after CoCl2 administration or subsequent HO-1 induction. We speculate that neonatal rats induce hepatic HO-1 and up-regulate ferritin by different mechanisms than do adult rats.
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PMID:Hepatic heme oxygenase is inducible in neonatal rats during the early postnatal period. 882 79

Heme oxygenase (HO) is the rate-limiting enzyme in the production of bilirubin from heme, and HO-1 is its inducible isoenzyme. In the metabolic pathway of HO a potential oxidant, heme, is degraded, a potential antioxidant, bilirubin, is generated, and a potent sequestering agent of redox active iron, ferritin, is thought to be coinduced. Therefore, the sum of the reactions of HO may be useful in antioxidant defense. To explore the role of HO in protection against oxidative stress, we examined HO-1 expression in Chinese hamster fibroblasts (HA-1) as well as stable hydrogen peroxide (H2O2)-resistant (OC-14) and 95% O2-resistant (O2R95) variant cell lines derived from HA-1, after exposure to 72 h of hyperoxia (95% O2-5% CO2). Total HO activity, HO-1 protein, and HO-1 mRNA steady-state levels were assessed before exposure and daily during exposure to hyperoxia. Controls were exposed to 95% air-5% CO2. Confluent monolayers of O2R95 and OC-14 cells had increased basal immunoreactive HO-1 protein levels relative to HA-1 cells when the cells were grown in normoxia, and O2R95 had higher total basal HO activity. When exposed to hyperoxia for up to 3 days, O2R95 cells, which were resistant to oxygen-induced killing, did not show induction of HO-1 mRNA or increased immunoreactive protein, whereas OC-14 and HA-1, which were relatively more sensitive than O2R95 to oxygen-related cytotoxicity, demonstrated significant increases in HO-1 expression during exposure to hyperoxia. Basal ferritin protein levels were highest in the O2R95 cells, intermediate in OC-14, and lowest in HA-1, but ferritin protein did not increase further, with hyperoxic exposure, in any of the cell lines. We conclude that increased constitutive HO-1 expression is associated with resistance to hyperoxia, whereas induction of HO-1 mRNA is an index of oxidative injury, since it only occurs after cells have sustained cytotoxic injury. We also conclude that increased ferritin expression does not necessarily accompany increased HO-1 expression in oxidant stress. We speculate that HO-1 plays a role in protection against hyperoxic damage.
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PMID:Differences in basal and hyperoxia-associated HO expression in oxidant-resistant hamster fibroblasts. 889 16

Heme formation in immature erythroid cells is subject to end-product negative feedback control. Although studies with immature erythroid cells obtained from animals have shown that increased intracellular hemin inhibits the acquisition of iron from transferrin, our experiments with human reticulocytes indicate that feedback inhibition of heme biosynthesis is primarily regulated at one or more steps that lead to formation of the first committed precursor, delta-aminolevulinate (ALA). To identify the site of control of heme biosynthesis in the human erythron further, region-specific antibodies to human erythroid delta-ALA synthase (e-ALA synthase) were used to immunoprecipitate newly-synthesised enzyme from human reticulocytes after biosynthetic labelling. Low concentrations of exogenous hemin (30-35 microM) inhibited the biosynthetic labelling of mature erythroid ALA synthase that was detected by exon 4 peptide-specific antibodies and antibodies raised against the entire recombinant human erythroid ALA synthase molecule. Pulse-chase experiments after biosynthetic labelling indicated no differences in the effect of hemin on the turnover of the radiolabelled enzyme and hemin did not influence the distribution of precursor froms of the ALA synthase molecule. Parallel experiments using antibodies directed against human H-chain ferritin confirmed the specificity of the effects of hemin on translation of the e-ALA synthase mRNA. At the concentrations of hemin used to inhibit heme formation from 14C-glycine, no significant effects on the rate of overall protein synthesis were observed. We conclude that heme regulates synthesis of the first committed precursor of the porphyrin biosynthetic pathway in immature human erythroid cells by effects on the synthesis of the e-ALA synthase molecule. Although the mechanism of hemin action is unknown, it is apparently independent of 5'-iron-response elements and influences the translational activity of erythroid ALA synthase mRNA.
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PMID:Translational control of erythroid delta-aminolevulinate synthase in immature human erythroid cells by heme. 907 95

Iron absorption from the whole diet, which contained a highly bioavailable form of iron, was measured for 5 d in 31 health men, including 12 blood donors. Nonheme iron in all meals was labeled with an extrinsic, inorganic radioiron tracer added in amounts to ensure uniform specific activity in all meals. Heme iron was labeled similarly by using hemoglobin biosynthetically labeled with another radioiron tracer. There was a good inverse relation between total absorption and concentration of serum ferritin up to approximately 60 micrograms/L. In subjects with serum ferritin > 60 micrograms/L there was no relation to iron absorption. At this serum ferritin concentration, absorption decreased to a level just sufficient to cover basal iron losses, implying that at a serum ferritin concentration > or = 60 micrograms/L no further accumulation of iron stores will occur by dietary iron absorption. The findings thus suggest that in normal subjects there is no risk of developing iron overload by iron absorption from the diet even if the diet is fortified. Similar findings were made previously in two studies in women, both of which indicated an effective control of absorption. At the same serum ferritin concentration the absorption per kilogram body weight was the same in men and women served identical diets with a high iron bioavailability. These new observations strongly suggest that translation of serum ferritin concentration into amounts of stored iron should be made with caution and that in subjects with high serum ferritin concentrations, other causes than increased iron stores should be considered. There was effective control of both heme- and nonheme-iron absorption but their relations to iron status were different.
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PMID:Iron absorption from the whole diet in men: how effective is the regulation of iron absorption? 939 7

Heme oxygenase (HO) proteins are members of the HSP30 family and consist of 2 isozymes identified to date, termed HO-1 and HO-2. Separate genes encode the isozymes and protein products which are immunochemically distinct, share less than 50% similarity at the amino acid sequence level. Each form, however, shows greater than 90% similarity among species, including human and the rat (reviewed in ref.). Furthermore, these isozymes function in a well-defined role to carry out oxidation of the heme molecule (Fe-protoporphyrin IX) in concert with NADPH-cytochrome P450 reductase. The oxidation of heme is isomer specific and results in the formation of bile pigments, carbon monoxide, and iron. The heme molecule constitutes the prosthetic moiety of hemoproteins, such as hemoglobin, myoglobin, catalase, soluble guanylate cyclase, cytochrome b5, cytochromes P450 and NO synthase. HO-1 also known as heat shock protein (HSP) 32 is encoded by a gene which is exquisitely stress-responsive and a host of stimuli that mediate oxidative stress cause induction of the protein both in vivo and in vitro. The HO-2 form shows a unique pattern of regulation from that of HO-1. HO-2 is a constitutive protein and its expression is not affected by the inducers of HO-1 tested to date; rather, the only known regulator of HO-2 yet identified is adrenal glucocorticoids. The two isozymes display vast differences in tissue distribution and under normal conditions HO-1 is present in the whole brain at the limit of immunodetection and is discreetly localized in select neuronal populations. HO-1 protein (approximately 32 kDa) and its approximately 1.8 kb transcript are increased, however, in response to stressful stimuli primarily in non-neuronal cell populations. The heme oxygenase system serves in both a catabolic and anabolic capacity in the cell. In the former capacity, it down-regulates cellular heme and hemoprotein levels. And, as such it inactivates the most effective catalyst for formation of free radicals, the heme molecule. In its anabolic role, as noted above, heme oxygenase produces bile pigments, carbon monoxide, and iron, all of which are biologically active: bile pigments function as antioxidants; the carbon monoxide generated by HO activity has been correlated with the generation of cGMP; and iron regulates expression of various genes, including that of HO-1 itself, as well as transferrin receptors, ferritin, and NO synthase. We used rabbit anti-rat HO-2 polyclonal antibody and HO-2 cDNA to localize HO-2 immunoreactive protein and the 1.3- and 1.9 kb homologous transcripts, respectively, in rodent brain as visualized by histochemical staining procedures. These protocols provide the first detailed description of methodologies successfully used to define the pattern of HO-2 expression at the transcriptional and translational levels in the adult rat brain and glucocorticoid-treated newborn rats. The procedures described herein have the virtue of being non-radioactive, as well as applicability to the systemic organs, such as the cardiovascular system and the male reproductive organs. Visualization of cellular HO-2 expression aids in assessment of potential sites of carbon monoxide, iron, and bilirubin production within the nervous system.
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PMID:Histochemical localization of heme oxygenase-2 protein and mRNA expression in rat brain. 938 81

Heme oxygenase (HO) activity leads to accumulation of the antioxidant bilirubin, and degradation of the prooxidant heme. Moderate overexpression of the inducible form, HO-1, is associated with protection against oxidative injury. However, the role of HO-2 in oxidative stress has not been explored. We evaluated survival, indices of oxidative injury, and lung and HO expression in HO-2 null mutant mice exposed to > 95% O2 compared with wild-type controls. Similar basal levels of major lung antioxidants were observed, except that the knockouts had a twofold increase in total glutathione content. Despite increased HO-1 expression from HO-1 induction, knockout animals were sensitized to hyperoxia-induced oxidative injury and mortality, and also had significantly increased markers of oxidative injury before hyperoxic exposure. Furthermore, during hyperoxia, lung hemoproteins and iron content were significantly increased without increased ferritin, suggesting accumulation of available redox-active iron. These results demonstrate that the absence of HO-2 is associated with induction of HO-1 and increased oxygen toxicity in vivo, apparently due to accumulation of lung iron. These results suggest that HO-2 functions to augment the turnover of lung iron during oxidative stress, and that this function does not appear to be compensated for by induction of HO-1 in the knockouts.
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PMID:Oxygen toxicity and iron accumulation in the lungs of mice lacking heme oxygenase-2. 948 70

Epidemiologic studies have found a relation between body iron stores and risk of chronic disease. Iron-absorption studies from single meals have shown that many dietary factors can influence nonheme-iron bioavailability. However, little is known about the association of these dietary factors with iron stores in free-living elderly populations. To address this question, we investigated the consumption of various dietary components and iron stores in an elderly sample of The Framingham Heart Study participants. Serum ferritin was used as a measure of body iron stores in 634 free-living elderly (67-93 y of age), and dietary intake during the previous year was assessed by a food-frequency questionnaire. The relation between serum ferritin and various dietary factors was assessed by multiple regression analysis. Subjects whose ferritin concentrations might be pathologically elevated because of infection, inflammation, liver disease, or genetic hemochromatosis were excluded from the analysis. After we controlled for sex, age, body mass index, total energy intake, smoking, and use of aspirin and other medications known to affect blood loss, we found five significant dietary factors associated with iron stores. Heme iron, supplemental iron, dietary vitamin C, and alcohol were positively associated with serum ferritin, whereas coffee intake had a negative association. As expected, sex was a strong predictor of serum ferritin-women having significantly lower mean concentrations than men. However, age was not related to serum ferritin in our elderly population. Our results suggest that in typical Western-style diets, a small number of dietary factors probably modulate the bioavailability of dietary iron and influence the accumulation of iron stores.
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PMID:Dietary determinants of iron stores in a free-living elderly population: The Framingham Heart Study. 998 4


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