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Iron Metabolism: Iron Transport and Cellular Uptake Mechanisms
Published in Bo Lönnerdal, Iron Metabolism in Infants, 2020
Much attention has been given to the interaction of transferrin iron with transferrin receptors on cell membranes to provide a supply of iron for body cells.10,21 Biochemists have long speculated on the evolutionary advantage of the mammalian two-sited protein, and the questions of whether or not iron bound to the two sites of transferrin behaves in exactly the same way.4 A stimulus to such studies was the report by Fletcher and Huehns199 of nonhomogenous behavior of transferrin iron in a reticulocyte-incubation model. They suggested that one binding site preferentially delivers iron to the erythron while the other supplies nonerythroid tissues.199 A number of supportive studies followed, some demonstrating differences in the chemical behavior of the two sites and other espousing a nonuniform iron release to reticulocytes in vitro and to body tissues in vivo.74,200–205 Questions raised by these studies were answered only after the uptake and release of iron from the transferrin molecule were better understood.
Iron Deficiency Anemia
Published in Harold R. Schumacher, William A. Rock, Sanford A. Stass, Handbook of Hematologic Pathology, 2019
Donald P. Skoog, James R. Newland
As the deficiency progresses, under the stimulation of increasing amounts of erythropoietin, erythroid precursors are more numerous in the marrow, and the lack of iron causes the more mature forms to have visibly less cytoplasm that has deficient hemoglobinization. Anemia worsens, and progressively smaller red cells with lesser amounts of hemoglobin become more numerous in the peripheral blood. As the duration and severity of deficiency increase, and as more of the previously produced normal cells become senescent and are removed, the RDW increases and red cell histogram widens. The MCV and MCH decrease and become progressively more abnormal, in proportion with the decrease in hemoglobin. Likewise, there is a proportionate increase in serum transferrin receptors.
The Contribution of Iron and Transition Metal Micronutrients to Diabetes and Metabolic Disease
Published in Emmanuel C. Opara, Sam Dagogo-Jack, Nutrition and Diabetes, 2019
Lipika Salaye, Zhenzhong Bai, Donald A. McClain
By contrast to cells expressing high levels of ferroportin, cells with little or no ferroportin will accumulate iron when serum iron is high, be that in a low-hepcidin state such as HH or a high-hepcidin state such as dietary iron overload. Beta-cells do not express ferroportin, hence one would expect beta-cell dysfunction in both situations, and that is the case. Why the beta-cell would be especially sensitive to iron is not clear. Iron entry into cells is normally regulated at the level of the transferrin receptor, whose mRNA is downregulated when intracellular iron is high. However, when transferrin has higher levels of saturation, as in HH, there will be levels of free iron in blood that could enter cells through other, less-specific divalent metal transporters. It is reasonable to hypothesize that cells with high levels of such transporters, such as beta-cells that transport high amounts of zinc for condensation of insulin in secretory granules, might be especially vulnerable to high transferrin saturation. This might even explain the relatively increased prominence of beta-cell loss in HH compared to T2DM, due perhaps to the higher levels of Tf saturation in HH compared to dietary excess.
Potential of Application of Iron Chelating Agents in Ophthalmic Diseases
Published in Seminars in Ophthalmology, 2021
Alireza Ghaffarieh, Joseph B. Ciolino
The unavailability of iron limits microbial growth and impairs host resistance,11 including impaired lymphocyte mitogenic response12 and abnormalities in granulocyte function such as impaired phagocytosis, abnormal bactericidal activity, respiratory burst, and myeloperoxidase activity.13–15 The antibacterial effect of cytokines is mediated by intracellular iron depletion. In response to several cytokines such as interferon (INF)-γ, IL-1, and tumor necrosis factor (TNF), the cell depletes its intracellular metabolically active iron pool by enhancing ferritin synthesis. This may result in a shift of cellular iron into the relatively inert ferritin storage compartment.16,17 It causes down-regulation of transferrin receptor production, decreasing cellular iron uptake and limiting iron availability for intracellular pathogens.18,19 Activation of nitric oxide synthesis and formation of iron-sulfur-nitric oxide complexes inactivates iron-sulfur centers of vital cellular enzymes.20 It has been demonstrated that the antibacterial effect of cytokines may be reversed by iron therapy and potentiated by deferoxamine treatment.20
Surface-modified polymeric nanoparticles for drug delivery to cancer cells
Published in Expert Opinion on Drug Delivery, 2021
Arsalan Ahmed, Shumaila Sarwar, Yong Hu, Muhammad Usman Munir, Muhammad Farrukh Nisar, Fakhera Ikram, Anila Asif, Saeed Ur Rahman, Aqif Anwar Chaudhry, Ihtasham Ur Rehman
Different receptors are overexpressed on the surfaces of cancer cells due to a deficient supply of nutrients. Selective ligands are attached to the surfaces of nanoparticles to deliver drugs in cancer cells via receptor–ligand interaction [206]. Here, two surface receptors, i.e., transferrin and folate are mentioned, which are highly expressed on the surfaces of cancer cells and can be utilized for anticancer drug delivery through the cell membrane. Transferrin receptor is a glycoprotein and works for cell growth and iron homeostasis. It is overexpressed in different types of cancers. Many transferrin linked nanoparticles have been fabricated for drug delivery to cancer cells [87]. Folate receptors are also overexpressed in many cancer types to take much folic acid for their survival. Many researchers have conjugated folate on the surfaces of nanoparticles to transport anticancer drug via receptor-mediated endocytosis [207].
Ferritin L-subunit gene mutation and hereditary hyperferritinaemia cataract syndrome (HHCS): a case report and literature review
Published in Hematology, 2021
Yunfan Yang, Ting Lin, Pu Kuang, Xinchuan Chen
In August 2020, she visited the outpatient department of Hematology of West China Hospital for further assessment due to persistently raised serum ferritin. Repeated examination indicated that her serum ferritin concentration was significantly increased (1652 ng/ml, reference value 24–336 ng/ml). Further laboratory examination indicated that, except for a slight decrease in transferrin (2.26 g/L, reference value 2.5–4.3 g/L), other iron metabolism parameters including soluble transferrin receptor (1.16 mg/L, reference value: 0.76–1.76 mg/L), serum iron (22.4 umol/L, reference value: 7.8–32.2 umol/L), total iron-binding capacity (TIBC) (51.25 umol/L, reference value: 48.3–68.0 umol/L) and transferrin saturation (43.7%, reference value: 20%∼55%) were all normal. Evaluation of magnetic resonance imaging (MRI) of the heart and liver showed no evidence of parenchymal iron overload. She had no other aetiologies such as malignancy, inflammation, obesity, and alcohol abuse that could cause hyperferritinemia. Consequently, genetic testing was carried out on the patient.