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)

Iron is required for cellular life. However, abnormalities of its metabolism may lead to iron deficiency or iron overload, both conditions which are deleterious. Therefore, stock and distribution of iron in the body must be very stable. Classically, four major proteins are involved in iron metabolism: (a) transferrin which is implicated in its plasmatic transport, (b) transferrin receptor which regulates iron-transferrin uptake, (c) ferritin, the major iron storage protein, and (d) IRP (Iron Regulatory Protein) which regulates both the entry and storage of iron by linking to the IRE (Iron Responsive Element), a nucleotidic sequence found on transferrin receptor and ferritin mRNA. Thus, IRP adapts gene expression to the iron cellular status. Recent data give informations about new proteins involved in iron metabolism: HFE whose gene is mutated in genetic hemochromatosis, ceruloplasmin which permits cellular iron egress and frataxin which is implicated in the exit of iron from mitochondria.
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PMID:[Current data on iron metabolism]. 1052 Apr 10

In a previous study we found copper dyshomeostasis in patients with Alzheimer's disease. In this study, levels of copper in plasma, of ceruloplasmin in serum and ceruloplasmin oxidative activity as well as superoxide dismutase (SOD) activity in erythrocytes were determined in 40 patients with Parkinson's disease and their healthy age- and gender-matched controls. Copper concentrations did not differ significantly in the two groups, whereas both ceruloplasmin concentrations and ceruloplasmin oxidative activity were significantly lower in the patients, also relative to ceruloplasmin mass. SOD activity was not significantly different in the two groups but decreased significantly with the duration of disease. The same was found for ceruloplasmin oxidative activity. Ceruloplasmin oxidative activity and SOD activity did not decrease with age. Levels of serum iron, serum ferritin and total iron binding capacity were determined in about 30 of the patients and an equal number of controls and were not found to differ. Transferrin levels were significantly lower in the patients than in their controls but, conversely, the transferrin saturation was significantly higher in the patients. The results indicate that patients with Alzheimer's disease and Parkinson's disease have defective ceruloplasmin and SOD activities in common and that these defects are not necessarily associated with major disturbances in iron homeostasis.
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PMID:Copper, ceruloplasmin, superoxide dismutase and iron parameters in Parkinson's disease. 1060 87

Our objectives were to study the value of different proteins in the serum and ascitic fluid and assess their potential in discriminating between malignant and nonmalignant ascites in a model that could be developed to aid clinical diagnosis. In all, 57 different measurements (30 in serum and 27 in ascitic fluid) including erythrocyte sedimentation rate, number of white blood cells, cytokines, interleukin-1a (IL-1a), IL-1b, IL-2, IL-6, IL-8, tumor necrosis factor-alpha, immunoglobulins (IgG, IgA, IgM), complement factors C3 and C4, acute-phase proteins such as alpha1-acid glycoprotein, alpha2-macroglobulin, alpha1-antitrypsin, haptoglobin, C-reactive protein, ferritin, ceruloplasmin and transferin, were performed in 61 patients with ascites (25 with malignant exudates, 13 with nonmalignant exudates, and 23 with transudates). Patients with sepsis were excluded. Correlation tests and one-way ANOVAs were used for comparisons between different groups. Discriminant analyses were used to assess the significance of each parameter in the differentiation process. Correct classification of 100% of cases required the use of all 57 ascitic fluid measurements in the model, which was not considered practical in clinical diagnosis. Discriminant analysis showed that five ascitic fluid measurements-total protein, LDH, TNF-alpha, C4, and haptoglobin-were sufficient for a model to correctly classify 89% of cases. Cross-validation showed that 70% of unknown cases were correctly classified using this model. In conclusion, we have shown that five easily taken protein measurements in the ascitic fluid can differentiate to a large extent between cases with ascites and have proposed a relatively simple statistical model with these parameters that could be developed to be extremely useful in the clinical setting.
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PMID:Discrimination between malignant and nonmalignant ascites using serum and ascitic fluid proteins in a multivariate analysis model. 1074 24

We have previously reported several studies on the loading of iron into ferritin by ceruloplasmin using proteins from rats. Loading iron into human ferritin using human serum ceruloplasmin is complicated by the fact that human ceruloplasmin is very susceptible to proteolysis (T. P. Ryan, T. A. Grover, and S. D. Aust, 1992, Arch. Biochem Biophys. 293, 1-8). The present study investigated the effect of proteolysis on the ability of human ceruloplasmin to load iron into human ferritin. SDS-PAGE revealed one major band with an apparent molecular weight of 116 kDa for a proteolytically degraded form of ceruloplasmin versus a 132-kDa band for an intact form of the enzyme. Both forms of the enzyme possessed ferroxidase activity, although that of the proteolytically degraded enzyme was approximately twofold less than that of the intact enzyme (4.9 nmol (min)-1 vs 8.3 nmol (min)-1). Only the intact form of ceruloplasmin was able to catalyze iron loading into ferritin without altering the physical characteristics of the ferritin protein during the process. Abnormal migration in nondenaturing PAGE gels, as well as a decrease in the amount of detectable ferritin protein, was observed when ferritin was incubated with iron alone or with proteolytically degraded ceruloplasmin and iron. It was concluded that the structural integrity of ceruloplasmin is required for the enzyme to effectively catalyze iron loading into ferritin.
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PMID:Intact human ceruloplasmin is required for the incorporation of iron into human ferritin. 1101 27

The copper-binding protein ceruloplasmin oxidizes ferrous iron to ferric iron, an action that is critical for the binding of iron to transferrin in plasma. Ceruloplasmin, in common with ferritin and transferrin, is an acute-phase protein that is altered by inflammation. We sought to identify interrelationships between the copper and iron systems by measuring copper, ceruloplasmin, ferroxidase, ferritin, transferrin, iron, and iron-binding capacity in a group of hemodialysis patients. We looked for evidence of inflammation and free-radical injury by assaying for protein carbonyl groups, protein pyrrolation, di-tyrosine, and advanced oxidation protein products. Our findings were compatible with an active inflammatory state that affected both iron and copper metabolism. Transferrin levels were low, whereas ceruloplasmin levels were elevated compared to normal. Copper concentration was increased proportional to ceruloplasmin. Several variables including ceruloplasmin and transferrin were observed to correlate significantly with the level of pyrrolated protein. The data suggest that posttranslational modification of circulating proteins may affect their structural, enzymatic, and ligand-binding properties. Abnormalities in copper metabolism and their influence on iron handling in renal failure are complex and will require additional study before their importance can be defined.
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PMID:Relationships between the copper and iron systems in hemodialysis patients and variables affecting these systems. 1109 67

Twenty-two different protein measurements were taken in the serum and ascitic fluid of fifty consecutive patients in an attempt to investigate which tests are the most reliable for the differential diagnosis of ascites. Serum and ascitic fluid total proteins (TPR), albumin (ALB), lactate (LAC), ferritin (FER), C3 and C4 complement factors, C-reactive protein (CRP), ceruloplasmin (CER), alpha2-macroglobulin (alpha2MG), haptoglobin (HAP), alpha1-antitrypsin (alpha1AT), alpha1-acid glycoprotein (alpha1AG), transferrin (TRF), immunoglobulins IgG, IgA, IgM and cytokines such as interleukin-1alpha (IL-1alpha), interleukin-1beta (IL-1beta), interleukin-2 (IL-2), interleukin-6 (IL-6), interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-alpha) were measured to distinguish between malignant and cirrhotic ascites. Correlations and non-parametric Mann-Whitney tests were used for ascitic fluid:serum ratio comparisons between the two groups. Multivariate analyses were used to determine the most significant biochemical ratio predictors for the differential diagnosis and a recursive partitioning model was constructed. Highly positive correlations (r>0.50) were found between the ratios IgA, IgG, IgM, CER, alpha2 MG, HAP, alpha1AT, alpha1AG and TRF. There was evidence that TPR, ALB, LAC, FER, IgG, CER, alpha2MG, alpha1AT, alpha1AG, TRF and IL-8 ascitic fluid:serum ratios are significnatly higher in patients with malignant neoplasms than in cirrhotics. In the recursive partitioning model the most significant parameters were found to be the ratios of albumin and IL-1alpha. The model fitted allowed for 100% correct classification of ascites. In conclusion, we have shown that a simple and very accurate model based on two ascitic fluid: serum measurements is able to differentiate between malignant and non-malignant ascites.
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PMID:Use of a variety of biological parameters in distinguishing cirrhotic from malignant ascites. 1128 54

Ceruloplasmin, metallothionein, and ferritin are metal-binding proteins with potential antioxidant activity. Despite evidence that they are upregulated in pulmonary tissue after oxidative stress, little is known regarding their influence on trace metal homeostasis. In this study, we have used copper- and zinc-containing superoxide dismutase (Cu/Zn SOD) transgenic-overexpressing and gene knockout mice and hyperoxia to investigate the effects of chronic and acute oxidative stress on the expression of these metalloproteins and to identify their influence on copper, zinc, and iron homeostasis. We found that the oxidative stress-mediated induction of ceruloplasmin and metallothionein in the lung had no effect on tissue levels of copper, iron, or zinc. However, Cu/Zn SOD expression had a marked influence on hepatic copper and iron as well as circulating copper homeostasis. These results suggest that ceruloplasmin and metallothionein may function as antioxidants independent of their role in trace metal homeostasis and that Cu/Zn SOD functions in copper homeostasis via mechanisms distinct from its superoxide scavenging properties.
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PMID:Cellular response of antioxidant metalloproteins in Cu/Zn SOD transgenic mice exposed to hyperoxia. 1140 60

Recombinant human ferritin loaded with iron via its own ferroxidase activity did not sediment through a sucrose-density gradient as a function of iron content. Analysis of the recombinant ferritin by native PAGE demonstrated an increase in altered migration pattern of the ferritins with increasing sedimentation, indicating an alteration of the overall charge of ferritin. Additionally, analysis of the ferritin by SDS-PAGE under nonreducing conditions demonstrated that the ferritin had formed large aggregates, which suggests disulfide bonds are involved in the aggregation. The hydroxyl radical was detected by electron spin resonance spectroscopy during iron loading into recombinant ferritin by its own ferroxidase activity. However, recombinant human ferritin loaded with iron in the presence of ceruloplasmin sedimented through a sucrose-density gradient similar to native ferritin. This ferritin was shown to sediment as a function of iron content. The addition of ceruloplasmin to the iron loading assay eliminated the detection of the DMPO-*OH adduct observed during loading using the ferroxidase activity of ferritin. The elimination of the DMPO-*OH adduct was determined to be due to the ability of ceruloplasmin to completely reduce oxygen to water during the oxidation of the ferrous iron. The implications of these data for the present models for iron uptake into ferritin are discussed.
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PMID:Modification of ferritin during iron loading. 1159 84

This review examines the clinical consequences for the practicing hematologist of remarkable new insights into the pathophysiology of disorders of iron and heme metabolism. The familiar proteins of iron transport and storage-transferrin, transferrin receptor, and ferritin-have recently been joined by a host of newly identified proteins that play critical roles in the molecular management of iron homeostasis. These include the iron-regulatory proteins (IRP-1 and -2), HFE (the product of the HFE gene that is mutated in most patients with hereditary hemochromatosis), the divalent metal transporter (DMT1), transferrin receptor 2, ceruloplasmin, hephaestin, the "Stimulator of Fe Transport" (SFT), frataxin, ferroportin 1 and others. The growing appreciation of the roles of these newly identified proteins has fundamental implications for the clinical understanding and laboratory evaluation of iron metabolism and its alterations with iron deficiency, iron overload, infection, and inflammation. In Section I, Dr. Brittenham summarizes current concepts of body and cellular iron supply and storage and reviews new means of evaluating the full range of body iron stores including genetic testing for mutations in the HFE gene, measurement of serum ferritin iron, transferrin receptor, reticulocyte hemoglobin content and measurement of tissue iron by computed tomography, magnetic resonance imaging and magnetic susceptometry using superconducting quantum interference device (SQUID) instrumentation. In Section II, Dr. Weiss discusses the improved understanding of the molecular mechanisms underlying alterations in iron metabolism due to chronic inflammatory disorders. The anemia of chronic disorders remains the most common form of anemia found in hospitalized patients. The network of interactions that link iron metabolism with cellular immune effector functions involving pro- and anti-inflammatory cytokines, acute phase proteins and oxidative stress is described, with an emphasis on the implications for clinical practice. In Section III, Dr. Brissot and colleagues discuss how the diagnosis and management of hereditary hemochromatosis has changed following the identification of the gene, HFE, that is mutated in most patients with hereditary hemochromatosis, and the subsequent development of a genotypic test. The current understanding of the molecular effects of HFE mutations, the usefulness of genotypic and phenotypic approaches to screening and diagnosis and recommendations for management are summarized.
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PMID:Clinical Consequences of New Insights in the Pathophysiology of Disorders of Iron and Heme Metabolism. 1170 34

Insulin resistance syndrome (IRS) is a cluster of prevalent conditions including glucose intolerance, hypertension and dyslipidemia, which commonly predispose to cardiovascular disease. However, the mechanism by which IRS is related with cardiovascular disease is not yet settled. Recently, it has been hypothesized that atherosclerosis is an inflammatory disease and that an increase in oxidative stress plays a key role in causing endothelial dysfunction associated with atherosclerosis. There has been, however, no study directly relating IRS with oxidative stress in human subjects. We measured various markers of oxidative stress among subjects who participated in a population-based epidemiological study performed in 1996. IRS was defined as non-diabetic subjects having more than two of three salient features of the syndrome (glucose intolerance, hypertriglyceridemia/low high density lipoprotein (HDL)-cholesterol and hypertension). The subjects with IRS (n=70) showed higher plasma malondialdehyde (MDA; 2.10+/-1.43 vs. 1.63+/-1.21 micromol/ml, P=0.009), homocysteine (16.32+/-8.34 vs. 13.06+/-6.49 micromol/l, P=0.002) and ceruloplasmin concentrations (29.80+/-5.28 vs. 27.39+/-5.10 mg/dl, P=0.002) than control subjects (n=196). Plasma MDA concentration was positively correlated with waist-to-hip ratio (r=0.124, P=0.044), and with plasma triglyceride (TG; r=0.163, P=0.008), ferritin (r=0.200, P=0.002) and homocysteine concentrations (r=0.136, P=0.032). These results suggest that increase in oxidative stress may contribute to the development of cardiovascular disease in IRS.
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PMID:Oxidative stress markers in Korean subjects with insulin resistance syndrome. 1173 6


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