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)

Hemoglobin (Hb) induces heme oxygenase-1 (HO-1), which catalyzes the breakdown of heme to bilirubin, and ferritin. Rats pretreated with Hb have been shown to survive lethal doses of lipopolysaccharide (LPS; see L. Otterbein, S. L. Sylvester, and A. M. Choi. Am. J. Respir. Cell Mol. Biol. 13: 595-601, 1995). The physiological basis of this increased survival and the mechanism(s) involved in the protection against LPS by Hb are unknown. Here we investigated 1) the effects of Hb on the hemodynamic and biochemical parameters of LPS-induced tissue injury and 2) the mechanism(s) by which Hb conferred protection against shock and tissue injury. Hb-treated rats maintained normal mean arterial blood pressure, whereas control rats experienced cardiovascular collapse after a lethal dose of LPS. Hepatic and renal functions, peripheral white blood cells, serum lactate dehydrogenase, and phosphate also remained normal after LPS in Hb-treated rats. Hb also attenuated LPS-induced neutrophil alveolitis and tumor necrosis factor-alpha levels. Pretreatment with both desferoxamine, which, like ferritin, can bind iron, and with exogenous apoferritin failed to protect against LPS. In contrast, treatment with Hb plus desferoxamine, which induced HO-1 but not ferritin, did protect against LPS. Treatment with iron-dextran, which induced ferritin but not HO-1, did not protect against LPS. We conclude that Hb pretreatment reduces the inflammatory and physiological consequences of LPS and that the Hb-induced protection against LPS is dependent on HO-1 and not ferritin induction.
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PMID:Mechanism of hemoglobin-induced protection against endotoxemia in rats: a ferritin-independent pathway. 912 78

We report a 35-year-old man, who had been diagnosed with Weber-Christian disease, presented with acute onset of high fever, malaise, jaundice and hepatosplenomegaly with subcutaneous nodules. Laboratory tests showed elevated serum ferritin and liver enzymes, especially lactate dehydrogenase (LDH), with pancytopenia and coagulation abnormalities. Peripheral blood and bone marrow examinations showed erythro-, leuko- and thrombo-phagocytic histiocytes and macrophages. The patient developed the same clinical features seven years ago. Based on diagnosis of cytophagic histiocytic panniculitis, the patient was treated with steroid pulse therapy and oral cyclosporin A. The combination therapy caused a marked improvement in the clinical condition.
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PMID:A case of cytophagic histiocytic panniculitis: successful treatment of recurrent attacks with steroid pulse therapy and oral cyclosporin A. 925 59

Serum ferritin (SF) and lactate dehydrogenase (LDH) was estimated in 117 patients presenting with a breast lump and in 40 controls. Both pre and post treatment values were determined. Both the values were significantly higher in breast malignancies (p = 0.00) and also corresponded with the clinical stage and bulk of the tumour. The fall in post treatment values was proportional to the response to therapy. Persistent rise in values in the post treatment period was indicative of local recurrence of metastasis.
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PMID:Significance of serum ferritin and lactate dehydrogenase in benign and malignant disease of breast. 935 1

Searching to define diagnostic criteria for malignant and non-malignant pleural effusions, the differential diagnostic value of ferritin (FRT), haptoglobin (Hp), alpha 1-antitrypsin (alpha 1-AT), lactate dehydrogenase (LDH) and complement factors C3 and C4 were investigated prospectively in 100 consecutive patients with pleural effusions of various aetiologies. Pleural effusion FRT, C3 and C4 concentrations were found to be useful in differentiating exudates from transudates, so that transudates practically could be excluded in pleural effusion: serum FRT ratio lower than 0.5 and/or in pleural effusion values for C3 and C4 higher than 300 mg dl-1 and 70 mg dl-1, respectively. A pleural effusion: serum C3 ratio greater than 2 is seen only in malignant effusions. No discriminative pleural: serum ratio could be found in FRT and C4 values capable of differentiating malignant from non-malignant effusions. Pleural effusion alpha 1-AT and LDH values were elevated in exudates, as compared with transudates, and had an excellent sensitivity and predictive value, but low specificity, in differentiating malignant from non-malignant effusions. Finally, the sensitivity, specificity and positive predictive value of pleural effusion Hp concentrations were lower than those of FRT and complement factors C3 and C4, respectively.
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PMID:Diagnostic value of ferritin, haptoglobin, alpha 1-antitrypsin, lactate dehydrogenase and complement factors C3 and C4 in pleural effusion differentiation. 941 51

Astrocytes provide a vital protective function in the brain. These cells are also vulnerable to oxidative stress, thus their loss of function could contribute to neurodegeneration. The goal of this study is to develop a cell culture model to study oxidative stress in astrocytes. Enriched astrocytic cultures were generated from neonatal mice. tertiary-butyl hydroperoxide (t-bOOH) was used as an exogenous peroxide and lactate dehydrogenase (LDH) release as a measure of loss of viability. Exposure to t-bOOH resulted in a linear increase in astrocytic death reaching 91.2% after 4 h exposure. That cell death was due to oxidative injury, was shown by the ability of the antioxidant N,N'-diphenyl-1,4-phenylenediamine (DPPD) to protect the t-bOOH treated cells. The involvement of iron in cell toxicity was demonstrated by the ability of the iron specific chelator desferal (DF) to completely prevent t-bOOH induced LDH release. Cells treated with a lipid soluble iron compound 3,5, 5-trimethyl (hexanoyl) ferrocene (TMH-Ferrocene), were more vulnerable to t-bOOH whereas neither ferrous ammonium sulfate (FAS) nor ferric ammonium citrate (FAC) had an effect. The increased sensitivity of the cells exposed to TMHF was reversible with the iron chelator desferal. Addition of recombinant human heavy chain ferritin or human apo-transferrin (Tf) did not alter LDH release. Electron microscopic analysis indicated astrocytes exposed to t-bOOH exhibited mitochondrial swelling prior to cell death (lactate dehydrogenase release). Additional increases in mitochondrial swelling were seen when the astrocytes were exposed to the lipophilic iron compound TMH-ferrocene and t-bOOH. These studies show that astrocytes are exquisitely sensitive to oxidative stress and that their vulnerability is related to and enhanced by iron. Decreased mitochondrial function in response to oxidative stress may precede cell death.
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PMID:An in vitro model for analysis of oxidative death in primary mouse astrocytes. 955 79

Two patients with lysinuric protein intolerance (LPI) had near-fatal generalized varicella infection with severe interstitial pneumonitis, hepatitis, decreased platelet count, bleeding and hypoalbuminaemia. Active haemolysis resulted in anaemia and massive haemoglobinuria. Serum lactate dehydrogenase activity and ferritin concentration, which in patients with LPI in normal circumstances exceed the upper reference values 3-folds to 10-fold, increased to > 10,000 U/L and > 10,000 micrograms/L, respectively. The patients were treated with fresh frozen plasma, red-cell transfusions and intravenous acyclovir for 14 days, and recovered clinically in a month. Retrospectively, 3 of the 32 other known Finnish patients with LPI had had varicella infection that had been more severe than that in the other children in the family or in subjects in the neighbourhood and had led to hospital admission. Varicella antibodies were measured in 24 patients; 5 had no antibodies and 5 had very low antibody titres. Primary vaccination of three patients with living varicella vaccine increased antibody titres measurably in one patient. We suggest that patients with LPI who have no varicella zoster antibodies should be treated with acyclovir if exposed to varicella and should be (re)vaccinated against chickenpox.
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PMID:Varicella and varicella immunity in patients with lysinuric protein intolerance. 958 61

We tested a new synthetic, 8-hydroxyquinoline-based, hexadentate iron chelator, O-Trensox and compared it with desferrioxamine B (DFO). Iron mobilisation was evaluated: (i) in vitro by using ferritin and haemosiderin; DFO mobilised iron much more rapidly from ferritin at pH 7.4 than did O-Trensox, whereas at pH 4, ferritin and haemosiderin iron mobilisation was very similar with both chelators; (ii) in vitro by using cultured rat hepatocytes which had been loaded with 55Fe-ferritin; here DFO was slightly more effective after 100 hr than O-Trensox; (iii) in vivo administration i.p. to rats which had been iron-loaded with iron dextran; O-Trensox mobilised 51.5% of hepatic iron over two weeks compared to 48.8% for DFO. We also demonstrated the effect of O-Trensox in decreasing the entry of 55Fe citrate into hepatocyte cultures. The protective effect of O-Trensox against iron toxicity induced in hepatocyte cultures by ferric citrate was shown by decreased release of the enzymes lactate dehydrogenase (LDH), aspartate aminotransferase (AST), and alanine aminotranferase (ALT) from the cultures and, using electron paramagnetic resonance (EPR) measurements, decreased production of lipid radicals. O-Trensox was more effective than DFO in quenching hydroxyl radicals in an acellular system.
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PMID:Iron mobilisation and cellular protection by a new synthetic chelator O-Trensox. 971 98

Previous studies have demonstrated that altering the fatty acid composition of porcine pulmonary artery endothelial cells (PAEC) significantly modulates their susceptibility to oxidative stimuli, e.g. H2O2. Based on observations that fatty acids also function to transport iron, an important catalyst for H2O2-mediated hydroxyl radical generation, we hypothesized that fatty acid-induced alterations in PAEC iron metabolism contribute to modulation of PAEC oxidant susceptibility. To test this hypothesis, PAEC were treated with culture medium supplemented with 0.1 mM oleic (18:1), linolenic (18:3) or docosahexaenoic (22:6) acids or with an equivalent volume of ethanol vehicle for 3 h. After thorough washing and incubation in unsupplemented culture medium for 24 h, PAEC monolayers were subjected to additional studies. Supplementation with 22:6 attenuated lactate dehydrogenase (LDH) release from PAEC 2 h following treatment with 100 microM H2O2 for 30 min (% LDH release: ETOH-control = 7.9 +/- 1.6, 22:6-control = 5.9 +/- 0.9, ETOH-H2O2 = 26.4 +/- 4.2, 22:6-H2O2* = 16.2 +/- 2.9; *P < 0.05 vs ETOH-H2O2). In a non-cellular system, 18:1 and 18:3 were more effective than their methyl ester derivatives or 22:6 at translocating iron from aqueous to hydrophobic environments. In contrast, only supplementation with 22:6 significantly increased PAEC uptake of 57Fe and human umbilical vein endothelial cell (HUVEC) ferritin content, whereas none of the supplementation conditions altered PAEC catalytic iron measured with bleomycin. These novel observations indicate that specific fatty acids are capable of altering PAEC iron uptake and ferritin content thereby contributing to the understanding of the mechanisms by which fatty acids modulate the oxidant susceptibility of vascular endothelial cells.
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PMID:Attenuation of oxidant-mediated endothelial cell injury with docosahexaenoic acid: the role of intracellular iron. 977 76

Iron uptake by cells may increase the intracellular pool of prooxidant iron prior to storage of iron within ferritin. Because hyperoxia is toxic to alveolar macrophages (AM) via mechanisms involving oxidant stress, we hypothesized that iron uptake by AM might promote hyperoxia-induced injury. To assess this hypothesis, we cultured AM recovered from healthy volunteers under conditions of normoxia or hyperoxia (60% or 95% oxygen) in media of varying iron content, including control media (3 microM iron) and media supplemented with iron (FeCl3; total iron 10, 20, or 40 microM). AM injury was assessed by measuring release of lactate dehydrogenase (LDH), phagocytic activity for yeast, and cytosolic concentrations of calcium ([Ca2+]i) as determined by ratio image analysis of AM loaded with the fluorescent calcium probe indo-1. There was dose-dependent accumulation of iron and ferritin synthesis in AM exposed to iron-supplemented media. Exposure of AM to hyperoxia (60% and 95% oxygen, 18 h) in control media increased LDH release and impaired phagocytic activity for yeast; however, similar hyperoxic exposures in iron-supplemented media significantly increased the cells' LDH release and decreased phagocytosis. Exposure to 95% oxygen increased the [Ca2+]i of AM over 18 h, but similar exposure in iron-supplemented media induced greater increases in [Ca2+]i. As compared with exposure to normoxia, exposure to hyperoxia (60% and 95% oxygen) also decreased iron uptake and, to a greater extent, ferritin synthesis by AM in iron-supplemented media. These data suggest that: (1) iron uptake promotes hyperoxic injury to AM; and (2) hyperoxia impairs the capacity of AM to sequester iron in ferritin.
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PMID:Iron uptake promotes hyperoxic injury to alveolar macrophages. 987 25

We describe 4 cases of lysinuric protein intolerance, which all fulfilled the diagnostic criteria for hemophagocytic lymphohistiocytosis. Mature histiocytes and neutrophil precursors participated in hemophagocytosis in the bone marrow. Moreover, serum levels of ferritin and lactate dehydrogenase were elevated, hypercytokinemia was present, and soluble interleukin-2 receptor levels were increased up to 18.6-fold. The diagnosis of lysinuric protein intolerance should therefore be considered in any patient presenting with hemophagocytic lymphohistiocytosis.
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PMID:Intermittent hemophagocytic lymphohistiocytosis is a regular feature of lysinuric protein intolerance. 1063 91


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