Iron ferritin and

He Y, Lee T, Leong SK (1999) Time course of dopaminergic cell death and changes in iron, ferritin and transferrin levels in the rat substantia nigra after 6- hydroxydopamine (6-OHDA) lesioning. Free Radic Res 31 103-112. 

The Hp 2-2 phenotype is associated with higher serum iron, ferritin, and transferrin saturation, perhaps because of its preferential uptake by CD 163 receptors. Other possible clinical associations of the Hp polymorphism have been reviewed by Langlois and Delanghe. ... 

Alterations in the levels of iron, ferritin, and other trace metals in Parkinson s disease and other neurodegen-erative diseases affecting the basal ganglia. Brain 114 1953-1975. 

Hemoglobin, Iron, Ferritin and Transferrin in Serumj Iron in CSF... 

Koop H, Bachem MG (1992) Serum iron, ferritin, and Vitamin B12 during prolonged omeprazole therapy. J C/m Gastroenterol 14 288-292... 

Iron Absorption. A very important effect of ascorbic acid is the enhancement of absorption of nonheme iron from foods. Ascorbic acid also enhances the reduction of ferric iron to ferrous iron. This is important both in increasing iron absorption and in its function in many hydroxylation reactions (140,141). In addition, ascorbic acid is involved in iron metaboHsm. It serves to transfer iron to the Hver and to incorporate it into ferritin. 

Synthesis of the transferrin receptor (TfR) and that of ferritin are reciprocally linked to cellular iron content. Specific untranslated sequences of the mRNAs for both proteins (named iron response elements) interact with a cytosolic protein sensitive to variations in levels of cellular iron (iron-responsive element-binding protein). When iron levels are high, cells use stored ferritin mRNA to synthesize ferritin, and the TfR mRNA is degraded. In contrast, when iron levels are low, the TfR mRNA is stabilized and increased synthesis of receptors occurs, while ferritin mRNA is apparently stored in an inactive form. This is an important example of control of expression of proteins at the translational level. 

The protein that stores iron in the body is called ferritin. A ferritin molecule consists of a protein coat and an iron-containing core. The outer coat is made up of 24 pol3q5eptide chains, each with about 175 amino acids. As Figure 20-27 shows, the pol q5eptides pack together to form a sphere. The sphere is hollow, and channels through the protein coat allow movement of iron in and out of the molecule. The core of the protein contains hydrated iron(HI) oxide, FC2 O3 H2 O. The protein retains its shape whether or not iron is stored on the inside. When filled to capacity, one ferritin molecule holds as many as 4500 iron atoms, but the core is only partially filled under normal conditions. In this way, the protein has the capacity to provide iron as needed for hemoglobin s mthesis or to store iron if an excess is absorbed by the body. 

Nitric oxide has also been implicated in PD. Thus animals with MPTP-induced Parkinsonism not only show extensive gliosis in the substantia nigra (like humans) in which the glial cells produce NO, but Liberatore and colleagues have found that in iNOS (inducible nitric oxide synthase) knock-out mice the toxicity of MPTP is halved. Since NO releases iron from ferritin and produces toxic peroxinitrate in the presence of superoxide radicals it could accelerate, even if it does not initiate, dopaminergic cell death (see Hirsch and Hunot 2000 for further details). 

The release of iron from intracellular ferritin stores is thought to involve the reduction of Fe to Fe " (Funk et al., 1985) and one would expect this reduction to be fecilitated by the low oxygen tension, increased levels of reducing species and the low pH shown by nuclear magnetic resonance (NM to be as low as 6.9 after only 6 h of cold storage (Fuller et al., 1988). Exogenous redox-active quinones such as adriamycin have been shown to catalyse lipid peroxidation in the presence of ferritin under hypoxic conditions (Vile and Winterbourne, 1988), and lipid peroxidation is stimulated in micro-somes in the presence of purified ferritin and flavin... 

Vile, G.F. and Winterbourne, C.C. (1988). Adriamycin-dependent peroxidation of rat liver and heart microsomes catalysed by iron chelates and ferritin. Biochem. Pharmacol. 37, 2893-2897. 

Decreased RBC count, Hgb, and Hct Decreased serum iron level, TIBC, serum ferritin, and TSAT Decreased erythropoietin levels relative to the degree of hypoxia that is present... 

Iron Supplementation Use of ESAs can lead to iron deficiency if iron stores are not adequately maintained. If serum ferritin and TSAT fall below the goal levels, iron supplementation is required. Oral iron supplements are less costly than IV supplements and are generally the first-line treatment for iron supplementation. When administering iron by the oral route, 200 mg of elemental iron should be delivered daily to maintain adequate iron stores. 

Shirley, NY) sodium ferric gluconate (Ferrlecit by Watson Pharmaceuticals, Inc., Corona, CA) and iron sucrose (Venofer by American Reagent, Inc., Shirley, NY). Initiation of IV iron should be based on evaluation of iron stores. A serum ferritin level less than 100 ng/mL in conjunction with a TSAT level less than 20% indicates absolute iron deficiency and is a clear indication for the need for iron replacement.31 When TSAT is less than 20% in conjunction with normal or elevated serum ferritin levels, treatment should be based on the clinical picture of the patient, as serum ferritin is an acute phase reactant, which may become elevated with inflammation and stress. Iron supplementation may be indicated if Hgb levels are below the goal level. 

Dentchev, T, Hahn, P, and Dunaief, JL, 2005. Strong labeling for iron and the iron-handling proteins ferritin and ferroportin in the photoreceptor layer in age-related macular degeneration. Arch Ophthalmol 123, 1745-1746. 

In normal human subjects, some 25 % of total body iron (800-1000 mg) is present in the storage forms, mostly as ferritin. Whereas it is likely that all mammalian cell types contain some ferritin, haemosiderin in normal subjects is essentially restricted to cells of the reticuloendothelial system. Ferritin turns out to be almost universal in its distribution ferritin and ferritin-like proteins have been found in all organisms except for one or two archaebacteria. In contrast, haemosiderin has not been found to any extent outside of iron-loaded animals, except for a brief report of a phytosiderin in pea seeds (Laulhere et ah, 1989). 

It has been suggested (Bozzi et ah, 1997 Grant et ah, 1998) that Dps and E. inocua ferritin represent examples of a family of ancestral dodecameric protein which had as function to trap, but not to mineralize, metal ions, and that the ability to oxidize and mineralize iron efficiently and to form fourfold interactions came later. The hollow-cored dodecameric motif exemplified by Dps and E. inocua ferritin has clearly been adapted to a number of functions, since in addition to DNA binding and iron storage, other family members include a novel pilin, a bromoperoxidase and several other proteins of unknown function (Grant et ah, 1998). 

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