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)

Acutely, hemin sensitizes endothelial cells to oxidants but chronically protects the endothelium through the induction of ferritin. By releasing its heme, methemoglobin can sensitize endothelial cells in a fashion similar to free hemin. Furthermore, prolonged incubation with the endothelium allows methemoglobin to induce heme oxygenase and ferritin and concomitantly to modulate oxidant-mediated cytotoxicity. Methemoglobin but not hemoglobin, metmyoglobin or cytochrome c induces heme oxygenase and ferritin. Heme needs to be released from methemoglobin, since sodium cyanide, haptoglobin, and hemopexin inhibit the induction of these proteins. Neutrophils can oxidize hemoglobin to methemoglobin, which can subsequently induce both heme oxygenase and ferritin. We speculate that in shock with disseminated intravascular coagulation, marginated PMNs oxidize hemoglobin to heme-releasing methemoglobin. If critical defenses such as haptoglobin and hemopexin are overwhelmed, heme enters the endothelin cells, sensitizing them to oxidant damage. Endothelial cell adaptation via heme-induced heme oxygenase and ferritin production might limit ultimate progression to pulmonary and other vascular leak syndromes.
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PMID:Endothelial cell heme oxygenase and ferritin induction by heme proteins: a possible mechanism limiting shock damage. 130 86

In conclusion, many specialized tests for the evaluation of anemia and RBC abnormalities can readily be performed in-house or by commercial laboratories. Tests include RBC indices, examination of blood smears (for morphological changes, infectious agents, basophilic stippling, and polychromasia), reticulocyte counts, iron stains, serum iron determinations, Heinz body counts, and methemoglobin tests. These diagnostic tests should routinely be used for the evaluation of hematologic abnormalities that are detected by a CBC. Accurate interpretation of test results will provide vital information on the pathophysiological and/or etiologic mechanisms of disease and point the way to successful therapeutic intervention. Failure to adequately resolve some hematologic abnormalities, particularly in breeds in which heritable disease is a consideration, may require additional tests, including serum haptoglobin, ferritin and erythropoietin measurement, or assays for RBC enzymes, such as methemoglobin reductase, PK, and PFK. These tests usually are available only through research laboratories or hematology specialists, and it is advisable to consult with a veterinary clinical pathologist for referral to the appropriate individual or laboratory.
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PMID:Specialized hematology tests. 147 Jul 72

At typical imaging fields, the transverse relaxation rates 1/T2 of the protons of soft tissue are much greater than their longitudinal rates 1/T1. Because of this, clinical magnetic resonance images are generally collected using relatively short values of TR, an approach that both increases comfort for the patient and reduces medical costs. As a result, image contrast is dominated by the 1/T2 values of the tissue protons. Currently, small single-ion paramagnetic complexes--Gd-DTPA is the prime example--are being used to enhance contrast in clinical magnetic resonance imaging (MRI). However, such agents contribute comparably to 1/T1 and 1/T2 so that their utility is greatest when introduced into body fluids, for which 1/T1 and 1/T2 are also comparable; they are much less useful for enhancing contrast of soft tissue. For this, one must look elsewhere, to rather large aggregates of paramagnetic ions, which may either be paramagnetic or ferromagnetic. Iron in its many chemical and biochemical forms, both exogenous and endogenous, is important in this respect. Its presence in ferritin and hemosiderin--in excess in some diseases--is one example; deoxyhemoglobin in cells and methemoglobin in blood pools from trauma are others in which endogenous iron in several oxidation states is important. Magnetic particulates of various iron oxides are now being used as exogenous agents for enhancing 1/T2 preferentially at imaging fields. Predicting contrast enhancement under such circumstances can become rather complex, not because the theory is difficult, but because the underlying concepts are subtle.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Transverse relaxation (1/T2) of solvent protons induced by magnetized spheres and its relevance to contrast enhancement in MRI. 319 49

Isolated rat liver lysosomes were incubated with [14C]methemoglobin under various conditions. Optimal pH for the in vitro proteolysis was found to be 4-5. To evaluate whether or not degradation of added proteins could be due to enzyme leakage the integrity of the lysosomes was measured. Isolated lysosomes were found to be stable for up to 10 min of incubation at pH 5.5 and for 30 min at pH 7. The degradation of three different proteins (methemoglobin, ovalbumin, and lysozyme) was analyzed. No correlation was detected between rate of breakdown and physical properties of the proteins. Leupeptin, chloroquine, and propylamine inhibited proteolysis of added proteins by 45-65% in both neutral and acid milieu. Possible energy requirement was tested by the addition of Mg2+ and ATP to the incubation medium. A dose-dependent increase in proteolytic rate was found when ATP was added to the lysosomal suspension, a finding most likely due to acidification of the lysosomes and ensuing increased degradation. GTP and ITP were somewhat less effective. The noncleavable ATP analogue 5'-adenylylimidodiphosphate gave no stimulation. The ATP-driven proteolysis was inhibited by ethylmaleimide. Isolated lysosomes were also incubated with ferritin in order to visualize a possible uptake process of a protein in the electron microscope. Following incubation, ferritin particles were seen inside intralysosomal vesicles which appeared to be formed by invagination of the lysosomal membrane, a process designated microautophagy. The results thus support the notion that isolated lysosomes may micropinocytose and degrade exogenously added proteins and that this process is ATP dependent.
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PMID:Uptake--microautophagy--and degradation of exogenous proteins by isolated rat liver lysosomes. Effects of pH, ATP, and inhibitors of proteolysis. 396 51

Among the ferric compounds studied, cytochrome C, methemoglobin, lactoperoxidase, ferritin and ferric ion, in addition to catalase, had the ability to oxidize metallic mercury in the presence of hydrogen peroxide. On the other hand, hematin, the active center of catalase, did not oxidize metallic mercury. The results are consistent with the increased oxidation and uptake of mercury in the liver by acatalasemia mice.
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PMID:Mercury oxidation in vitro by ferric compounds. 711 84

Long term effects of the intracortical implantation of blood and blood products on the electrocorticogram were studied in cats and guinea pigs. Focal epileptiform paroxysmal discharges developed after implantation of whole blood, hemolyzed erythrocytes, methemoglobin, ferritin, ferrous chloride, ferric chloride, fibrinogen, hemin, and cottonoid. In each group recurrent paroxysmal discharges became more prominent and more frequent after several months, suggesting a physiological change caused by a breakdown product of blood. The lesions were characterized by varying degrees of cell loss, iron deposition and glial proliferation. It is thought that posttraumatic epilepsy, which is frequently accompanied by extravasation of blood into the brain, might share a similar physiopathogenesis.
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PMID:Effects of intracortical injection of blood and blood components on the electrocorticogram. 735 64

Iron-derived reactive oxygen species play an important role in the pathogenesis of various vascular disorders including vasculitis, atherosclerosis, and capillary leak syndromes such as the adult respiratory distress syndrome (ARDS). We have suggested that acute incorporation of the heme moiety of hemoglobin released from red blood cells into endothelium could provide catalytically active iron to the vasculature. Adaptation to chronic heme stress involves the induction of heme oxygenase and ferritin; the latter provides cytoprotection against free radicals in vitro. The present studies examine the bioavailability of heme, derived from hemoglobin, to induce heme oxygenase and ferritin in rat lungs in vivo. Intravenous injection of methemoglobin, but not oxyhemoglobin, increases total lung heme oxygenase mRNA approximately fivefold after 16 h. Accompanying this mRNA induction, expression of total lung heme oxygenase enzyme activity is also markedly enhanced. In situ hybridization for heme oxygenase reveals mRNA accumulation in the lung microvascular endothelium, implying incorporation of heme into endothelial cells. Similarly, methemoglobin significantly increases the ferritin protein content of rat lungs and in parallel, ferritin light-chain mRNA increases approximately 1.6-fold, whereas heavy-chain mRNA is upregulated by approximately 1.9-fold. Immunoreactive ferritin is present in lung microvascular endothelium after methemoglobin treatment, suggesting incorporation of heme iron into pulmonary vasculature. Subcutaneous injection of Sn-protoporphyrin IX, a competitive inhibitor of heme oxygenase, does not affect methemoglobin-induced ferritin synthesis in lungs. We speculate that methemoglobin, which might be generated by activated leukocytes in ARDS associated with disseminated interavascular coagulation, can provide heme iron to lung microvascular endothelium to induce heme oxygenase and ferritin.
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PMID:Endothelial cell heme oxygenase and ferritin induction in rat lung by hemoglobin in vivo. 786 52

Heme proteins transport oxygen and facilitate redox reactions. Heme, however, may be dangerous, especially when free in biologic systems. For example, iron released from hemoglobin-derived heme can catalyze oxidative injury to neuronal cell membranes and may be a factor in post-traumatic damage to the central nervous system. We have shown that heme catalyzes the oxidation of low density lipoproteins which can damage vascular endothelial cells. The endothelium is susceptible to damage by oxidants generated by activated phagocytes, and this has been invoked as an important mechanism in a number of pathologies including the Adulte Respiratory Distress Syndrome (ARDS), acute tubular necrosis, reperfusion injury and atherosclerosis. Because of its highly hydrophobic nature, heme readily intercalates into endothelial membranes and potentiates oxidant-mediated damage. This injury is dependent on the iron content of heme and is completely blocked when concomitant hemopexin is added. Ferrohemoglobin, when added to cultured endothelial cells, is without deleterious effects, but if oxidized to ferrihemoglobin (methemoglobin), it greatly amplifies oxidant damage. Methemoglobin, but not ferrohemoglobin, releases its hemes which can then be incorporated into endothelial cells. Cultured endothelial cells, when exposed to methemoglobin but not ferrohemoglobin, cytochrome c or metmyoglobin, potentiate this oxidant injury. Stabilization of the methemoglobin by cyanide, haptoglobin or capture of the heme by hemopexin abrogates this effect. Paradoxically, more prolonged exposure of endothelium to heme or methemoglobin renders them remarkably resistant to oxidant challenge. Endothelium defends itself from heme by induction of the heme degrading enzyme heme oxygenase and the concomitant production of large amounts of the iron binding protein ferritin.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Heme and the vasculature: an oxidative hazard that induces antioxidant defenses in the endothelium. 808 43

The appearance of intracranial hemorrhage at magnetic resonance (MR) imaging depends primarily on the age of the hematoma and the type of MR contrast (ie, T1 or T2 weighted). As a hematoma ages, the hemoglobin passes through several forms (oxyhemoglobin, deoxyhemoglobin, and methemoglobin) prior to red cell lysis and breakdown into ferritin and hemosiderin. Five distinct stages of hemorrhage can be defined: hyperacute (intracellular oxyhemoglobin, long T1 and T2), acute (intracellular deoxyhemoglobin, long T1, short T2), early subacute (intracellular methemoglobin, short T1, short T2), late subacute (extracellular methemoglobin, short T1, long T2), and chronic (ferritin and hemosiderin, short T2). The short T1 of methemoglobin is due to the paramagnetic dipole-dipole interaction. Another paramagnetic property, the magnetic susceptibility effect, is responsible for the short T2 observed when deoxyhemoglobin, methemoglobin, or hemosiderin is intracellular. T2 shortening can also be produced by hemoconcentration and clot retraction. The T2 shortening due to magnetic susceptibility effects is enhanced on higher-field-strength systems and on gradient-echo images and is reduced with "fast spin-echo" MR techniques.
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PMID:MR appearance of hemorrhage in the brain. 818 86

Iron-derived reactive oxygen species are implicated in the pathogenesis of various vascular disorders including atherosclerosis, vasculitis, and reperfusion injury. The present studies examine whether heme, when liganded to physiologically relevant proteins as in hemoglobin, can provide potentially damaging iron to intact endothelium. We demonstrate that reduced ferrohemoglobin, while relatively innocuous to cultured endothelial cells, when oxidized to ferrihemoglobin (methemoglobin), greatly amplifies oxidant (H2O2)-mediated endothelial-cell injury. Drawing upon our previous observation that free heme similarly primes endothelium for oxidant damage, we posited that methemoglobin, but not ferrohemoglobin, releases its hemes that can then be incorporated into endothelial cells. In support, cultured endothelial cells exposed to methemoglobin--in contrast to exposure to ferrohemoglobin, cytochrome c, or metmyoglobin--rapidly increased their heme oxygenase mRNA and enzyme activity, thereby supporting heme uptake; ferritin production was also markedly increased after such exposure, thus attesting to eventual incorporation of Fe. These cellular methemoglobin effects were inhibited by the heme-scavenging protein hemopexin and by haptoglobin or cyanide, agents that strengthen the liganding between heme and globin. If the endothelium is exposed to methemoglobin for a more prolonged period (16 hr), it accumulates large amounts of ferritin; concomitantly, and presumably associated with iron sequestration by this protein, the endothelium converts from hypersusceptible to hyperresistant to oxidative damage. We conclude that when oxidation of hemoglobin facilitates release of its heme groups, catalytically active iron is provided to neighboring tissue environments. The effect of this relinquished heme on the vasculature is determined both by extracellular factors--i.e., plasma proteins, such as haptoglobin and hemopexin--as well as intracellular factors, including heme oxygenase and ferritin. Acutely, if both extra- and intracellular defenses are overwhelmed, cellular toxicity arises; chronically, when ferritin is induced, resistance to oxidative injury may supervene.
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PMID:Endothelial-cell heme uptake from heme proteins: induction of sensitization and desensitization to oxidant damage. 841 93


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