Ferritins: A family of molecules for iron storage, antioxidation and more

Ferritins are characterized by highly conserved three-dimensional structures similar to spherical shells, designed to accommodate large amounts of iron in a safe, soluble and bioavailable form. They can have different architectures with 12 or 24 equivalent or non-equivalent subunits, all surrounding a large cavity. All ferritins readily interact with Fe(II) to induce its oxidation and deposition in the cavity in a mineral form, in a reaction that is catalyzed by a ferroxidase center. This is an anti-oxidant activity that consumes Fe(II) and peroxides, the reagents that produce toxic free radicals in the Fenton reaction. The mechanism of ferritin iron incorporation has been characterized in detail, while that of iron release and recycling has been less thoroughly studied. Generally ferritin expression is regulated by iron and by oxidative damage, and in vertebrates it has a central role in the control of cellular iron homeostasis. Ferritin is mostly cytosolic but is found also in mammalian mitochondria and nuclei, in plant plastids and is secreted in insects. In vertebrates the cytosolic ferritins are composed of H and L subunit types and their assembly in a tissues specific ratio that permits flexibility to adapt to cell needs. The H-ferritin can translocate to the nuclei in some cell types to protect DNA from iron toxicity, or can be actively secreted, accomplishing various functions. The mitochondrial ferritin is found in mammals, it has a restricted tissue distribution and it seems to protect the mitochondria from iron toxicity and oxidative damage. The various functions attributed to the cytosolic, nuclear, secretory and mitochondrial ferritins are discussed.

Arosio P, Ingrassia R, Cavadini P.
Dipartimento Materno Infantile e Tecnologie Biomediche, Università di Brescia, and A.O. Spedali Civili, Brescia, Italy

Ferritin: Dietary and stored iron as predictors of breast cancer risk

Increases in risk of breast cancer in successive generations of migrants to the United States from China and rapid temporal changes in incidence rates in China following social and economic changes clearly implicate environmental factors in the etiology of this disease. Case-control and cohort studies have provided evidence that at least some of these factors may be dietary. Iron, an essential element necessary for cell function, has also been demonstrated to have potential carcinogenic and co-carcinogenic activities.

Dietary and stored iron as predictors of breast cancer risk: A nested case-control study in Shanghai.

Iron overload, which was previously uncommon, has become more common in the United States than iron deficiency and may be increasing in China concurrently with dramatic increases in meat consumption. A case-control study nested in a cohort of women in Shanghai, China, was conducted to evaluate possible associations between risk of proliferative and nonproliferative fibrocystic changes as well as breast cancer and dietary iron intake and plasma ferritin levels.

Plasma ferritin levels and reported dietary iron intake were compared in 346 women with fibrocystic changes, 248 breast cancer cases and 1,040 controls. Increasing ferritin levels were significantly associated with increasing risk of nonproliferative fibrocystic changes (OR: 2.51, 95% CI: 1.16-5.45, p trend = 0.04). Similar, but weaker, trends were observed for proliferative changes and for breast cancer. Risk of breast cancer relative to the risk of fibrocystic changes was associated with dietary iron intake in women with nonproliferative fibrocystic changes (OR: 2.63, 95% CI: 1.04-6.68, p = 0.02).

In conclusion, this study finds significant associations between iron (stored and dietary) and fibrocystic disease and breast cancer

Department of Public Health and Preventive Medicine, Oregon Health and Sciences University, Portland, OR

The Usefulness of the Serum Transferrin Receptor to Serum Ferritin Ratio for Discriminating between Iron Deficiency Anemia and Anemia of Inflammation

BACKGROUND:
The incidence of iron deficiency anaemia in infants, which is caused by the increased iron demand for rapid growth during this period, is reported to range from 10 to 40%. This age group also suffers from a number of acute illnesses (urinary tract infection, pneumonia and other viral illness). The aim of this study was to evaluate the usefulness of soluble transferrin receptor (sTfR) values and the different methods of calculating the sTfR and serum ferritin (SF) ratio for differentiating anemia of inflammation (AI) from iron deficiency anemia (IDA) or a mixture of these two types of anemia.

METHODS:
173 infants among all the infants who visited Gyeongsang National University Hospital from 2000 to 2006 were enrolled in this study. The hemoglobin (Hb), SF and sTfR values were checked and the infants were divided into the Al subgroup (Hb <11g/dL and SF > 50microgram/L), the IDA subgroup (Hb <11g/dL and SF < 12microgram/L), the normal group (Hb > or =11g/dL and SF > or =12microgram/L), and the unclassified anemia (UCA) group (Hb <11g/dL and SF 12~50microgram/L).

RESULTS:
The mean sTfR and sTfR/Log SF values in the AI group were 3.89 and 10.6microgram/mL, respectively (P<0.01). These values in the IDA group were 1.9 and 36.11, respectively (P<0.01). The mean Log (sTfR/SF) was statistically significant between all the subgroups (1.35 in AI, 3.29 in IDA, 1.76 in Nor and 2.35 in UCA). All the infants in the IDA group had a Log (sTfR/SF) value >2.55 whereas all the infants classified in AI group had a Log (sTfR/SF) value <2.55.

CONCLUSION:
The Log (sTfR/SF) value is a useful criterion for discriminating between AI and IDA.