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)

Commercial preparations of ferritin inhibited reticulocyte-lysate cell-free protein synthesis and disaggregated polyribosomes to monoribosomes and ribosomal subunits. These effects were prevented by addition of reduced glutathione (GSH) to the incubation medium, but ferritin did not lower GSH concentration in the lysates. The more purified the ferritin preparation, the less inhibition of protein synthesis was observed. These data suggested that the effect was due to a contamination of the ferritin with proteolytic activity. In confirmation of this proposal we demonstrated that there was protease activity in both the 2X and 5X crystalized ferritin preparations, with 2.5 times greater activity in the 2X preparation. The proteolytic activity in ferritin was inhibited by incubation with the protease inhibitor tosyl lysine chloromethyl ketone (TLCK). When an amount of trypsin equivalent to the protease activity of the ferritin was added to the incubation mixture, similar effects on protein synthesis and the ribosome-polyribosome component were found. Both GSH and TLCK prevented these effects of trypsin. These data suggest that the previously reported effect of ferritin on reticulocyte cell-free protein synthesis was due to contamination of the ferritin by a protease. It appears that ferritin does not play a direct role in the pathogenesis of sideroblastic anaemias.
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PMID:Ferritin and sideroblastic anaemias: inhibition of protein synthesis by protease contaminants in commercial preparations of ferritin. 125 40

Hematopoietic stem cells are capable of self-replication and differentiation to lineage-committed progenitor cells. The progenitors proliferate and differentiate to lineage-specific, morphologically recognizable precursors and, finally, to terminal circulating blood cells. These homeostatic mechanisms are regulated by a complex set of interacting growth stimulatory and inhibitory factors that are produced by, or in collaboration with, the tissue's regulatory microenvironment. A number of well-characterized cytokines have been implicated in the negative regulation of hematopoiesis: ferritin H-subunit (HF), lactoferrin (Lf), prostaglandin E (PGE), tumor necrosis factor (TNF), interferon (IFN), transforming growth factor-beta (TGF beta), acetyl-N-Ser-Asp-Lys-Pro (AcSDKP) or thymosin-beta 4, pyroGlu-Glu-Asp-Cys-Lys (pEEDCK), macrophage inflammatory protein-1 alpha (MIP-1 alpha), inhibin, superoxide dismutase (SOD), glutathione (GSH) and others not well-known yet. The role of inhibitors in restraining stem cells from entering the cell cycle and protecting them from the toxic side effects of chemotherapeutic drugs is opening an alternate strategy for the treatment of cancer patients.
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PMID:[Biomolecules suppressing myelopoiesis]. 134 39

A number of xenobiotics are toxic because they redox cycle and generate free radicals. Interaction with iron, either to produce reactive species such as the hydroxyl radical, or to promote lipid peroxidation, is an important factor in this toxicity. A potential biological source of iron is ferritin. The cytotoxic pyrimidines, dialuric acid, divicine and isouramil, readily release iron from ferritin and promote ferritin-dependent lipid peroxidation. Superoxide dismutase and GSH, which maintain the pyrimidines in their reduced form, enhance both iron release and lipid peroxidation. Microsomes plus NADPH can reduce a number of iron complexes, although not ferritin. Reduction of Adriamycin, paraquat or various quinones to their radicals by the microsomes enhances reduction of the iron complexes, and in some cases, enables iron release from ferritin. Adriamycin stimulates iron-dependent lipid peroxidation of the microsomes. Ferritin can provide the iron, and peroxidation is most pronounced at low pO2. Complexing agents that suppress intracellular iron reduction and lipid peroxidation may protect against the toxicity of Adriamycin.
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PMID:Ferritin, lipid peroxidation and redox-cycling xenobiotics. 164 77

Incubation of rabbit heart microsomes with Adriamycin and NADPH resulted in the oxidation of approximately 25% of protein thiols and 66% inhibition of Ca-ATPase activity. Thiol oxidation and Ca-ATPase inactivation were iron-dependent and could be catalysed by ferritin. Removal of contaminating catalase revealed that both processes required H2O2 which could be supplied by O2 under aerobic conditions. However, O2- was not involved. Butylated hydroxytoluene (BHT), alpha-tocopherol and beta-carotene inhibited lipid peroxidation of microsomes, but did not inhibit thiol oxidation or the inactivation of Ca-ATPase. Likewise, the hydroxyl radical scavengers benzoate, formate and mannitol were not inhibitory. Glutathione (GSH), however, prevented inactivation of Ca-ATPase. It is concluded that Adriamycin-enhanced redox reactions involving iron and H2O2 are responsible for oxidizing microsomal thiol groups and inhibition of Ca-ATPase. Disruption of Ca transport within the myocyte by this process could contribute to the cardiotoxicity of Adriamycin.
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PMID:Thiol oxidation and inhibition of Ca-ATPase by adriamycin in rabbit heart microsomes. 215 95

The diabetogenic action of alloxan is believed to involve oxygen free radicals and iron. Incubation of glutathione (GSH) and alloxan with rat liver ferritin resulted in release of ferrous iron as assayed by spectrophotometric detection of ferrous-bathophenanthroline complex formation. Neither GSH nor alloxan alone mediated iron release from ferritin. Superoxide dismutase (SOD) and catalase did not affect initial rates of iron release whereas ceruloplasmin was an effective inhibitor of iron release. The reaction of GSH with alloxan resulted in the formation of the alloxan radical which was detected by ESR spectroscopy and by following the increase in absorbance at 310nm. In both instances, the addition of ferritin resulted in diminished alloxan radical detection. Incubation of GSH, alloxan, and ferritin with phospholipid liposomes also resulted in lipid peroxidation. Lipid peroxidation did not occur in the absence of ferritin. The rates of lipid peroxidation were not affected by the addition of SOD or catalase, but were inhibited by ceruloplasmin. These results suggest that the alloxan radical releases iron from ferritin and indicates that ferritin iron may be involved in alloxan-promoted lipid peroxidation.
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PMID:Alloxan- and glutathione-dependent ferritin iron release and lipid peroxidation. 253 98

A deficiency of choline and methionine is hepatocarcinogenic and is associated with an apparent increase in lipid peroxidation. In this study the susceptibility of microsomes and nuclei to ferritin-dependent lipid peroxidation is examined together with the status of the peroxidation-protective systems. Choline-methionine deficiency caused an increase in Se-independent GSH peroxidases (GSH transferase subunit 2) and membrane vitamin E but a decrease in Se-dependent GSH peroxidase and microsomal GSH peroxidase activity. Choline-methionine deficient microsomes and nuclei were 4-fold more susceptible to lipid peroxidation induced in vitro by physiological concentrations of ferritin/ascorbate/ADP; and the peroxidation was less effectively inhibited by GSH and soluble GSH peroxidases than controls. The results indicate that a decreased level of Se-dependent and membrane GSH peroxidases is involved in the increase in lipid peroxidation observed in choline-methionine deficiency.
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PMID:Lipid peroxidation in choline-methionine deficiency. 350 37

Basic red cell ferritin (RCF) content reflects the rate of iron uptake by marrow erythroid cells in patients with anaemia due to chronic inflammation which are sometimes also associated with metabolic disorders of the erythrocytes. For 29 patients with active inflammatic states of chronic rheumatoid arthritis (RA) and microcytic (mean corpuscular volume up to 80fl) or normocytic (MCV 80-95fl) anaemia respectively, the mean RCF content, irrespective of plasma ferritin levels, was determined using a recently established ELISA test. Red cell intermediates (ATP, GSH, 2.3 DP.G) were measured using conventional methods. The results revealed decreased RCF levels (2.8 +/- 1.5 ag/RBC) in 12 patients with RA and normal values (8.8 +/- 4.7 ag/RBC) in 17 patients which obviously did not correlate with the degree of the anaemia. The extent and pattern of the intermediates of RBC did not significantly vary from normal values. Thus, ATP, GSH and 2.3 DPT levels of RBC were only slightly increased up to 10%, especially in those patients with higher anaemic degrees. The findings of our study suggest that conventional indices for iron metabolic disorder in anaemic patients with chronic inflammatic disease should include peripheral microcytosis, transferrin saturation, and RCF content but could neglect plasma ferritin concentrations. Concerning the RBC metabolism this study did not disclose any further influences on iron metabolism parameters due to changes of mean cell age in patients with RA. Specific alterations which might hence produce additional functional disturbances of the erythrocytes in the peripheral microcirculation thus leading further to tissue cell damages in RA could be excluded as well.
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PMID:Red cell metabolism and ferritin levels in iron deficiency anaemia. 359 1

The localization of gamma-Glutamyltransferase (gamma-GT, E.C.2.3.2.2) was studied on isolated tubular fragments from rat kidney cortex immunocytochemically. Monospecific antibodies raised in the goat against rat kidney gamma-GT were used. Antigoat immunoglobulin from the rabbit conjugated with ferritin was used for visualisation of the antibody binding sites. The enzyme was found to be localized at the brush border membrane of proximal tubules, the luminal membrane of distal tubules and collecting duct segments. The enzyme could further be localized on the antiluminal or basolateral cell membranes of proximal and distal tubular fragments, whereas no such localization was verified for collecting duct segments. The role of this basolateral gamma-GT localization in context with the kidney's ability to extract over 83% of the renal arterial glutathione (GSH) input during a single passage is discussed.
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PMID:Immunocytochemical localization of gamma-glutamyl-transferase on isolated renal cortical tubular fragments. 614 46

Acute iron loading of rats, by intraperitoneal administration of iron-dextran (500 mg Fe/kg body wt 18-20 h before killing) decreased by 30% the rate of conversion of 5-amino-[14C]levulinate ([14C]ALA) into heme as measured with a recently described procedure for liver homogenates (1981. Biochem. J. 198: 595-604). The decrease in conversion of labeled ALA into heme caused by iron loading was shown to be due to a 70-80% decrease in activity of ALA dehydrase. The decrease in activity of ALA dehydrase caused by iron loading was not associated with a decrease in hepatic concentrations of GSH, nor could it be reversed by addition of dithiothreitol, Zn2+ or chelators of Fe2+ and Fe3+. Addition of FeSO4, ferric citrate, or ferritin to homogenates of control liver had no effect of activity of ALA dehydrase. The decrease in activity of ALA dehydrase, caused by iron-dextran, was mirrored by a reciprocal increase in ALA synthase. Iron-dextran potentiated the induction of ALA synthase by allylisopropylacetamide. However, this potentiation could be dissociated from the decrease in ALA dehydrase caused by iron loading.
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PMID:Iron and the liver: acute effects of iron-loading on hepatic heme synthesis of rats. Role of decreased activity of 5-aminolevulinate dehydrase. 618 58

The effect of riboflavin supplementation (5mg twice daily for 8 weeks) on reduced blood glutathione (GSH) and iron status was assessed in 18 patients with sickle cell disease (SCD-HbSS). Twelve SCD patients and 13 normal (Hb-AA) subjects served as the control. The total iron binding capacity (TIBC) and serum ferritin (SF) were significantly higher (p < 0.01), but GSH level, haemoglobin and transferrin saturation (TS) were significantly lower (p < 0.001) in SCD patients than in normal subjects. The administration of riboflavin elicited a significant increase (p < 0.01) in serum iron and TS but a non significant increase in SF and circulating Hb. The GSH level varied little in riboflavin supplemented but decreased significantly in unsupplemented SCD. The disparity in GSH concentration might reflect availability of FAD for regeneration of GSH from glutathione. Likewise, the haematological improvement in the supplemented group supports the assertion that riboflavin enhances erythropoiesis. For an effective management of SCD in Africa, a closer attention should be directed to the riboflavin status in haemolytic disorders.
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PMID:Clinical trial of riboflavin in sickle cell disease. 829


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