Emerging and Dynamic Biomedical Uses of Ferritin
Abstract
:1. Ferritin Introduction
2. Ferritin as an Iron Delivery Protein
3. Ferritin as a Delivery Agent
4. Ferritin as a Mineralization Chamber
5. Ferritin as a Marker for Inflammation
6. Ferritin as a Disease Biomarker
6.1. Neuroferritinopathy
6.2. Parkinson’s Disease
6.3. Restless Legs Syndrome
6.4. Amyotrophic Lateral Sclerosis
7. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
- Laufberger, V. Sur la cristallisation de la ferritine. Bull. Soc. Chim. Biol. 1937, 19, 1575–1582. (In French) [Google Scholar]
- Bradley, J.M.; Le Brun, N.E.; Moore, G.R. Ferritins: Furnishing proteins with iron. J. Biol. Inorg. Chem. 2016, 21, 13–28. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Arosio, P.; Levi, S. Ferritin, Iron Homeostasis, and Oxidative Damage. Free Radic. Biol. Med. 2002, 33, 457–463. [Google Scholar] [CrossRef]
- Arosio, P.; Ingrassia, R.; Cavadini, P. Ferritins: A family of molecules for iron storage, antioxidation and more. Biochim. Biophys. Acta Gen. Subj. 2009, 1790, 589–599. [Google Scholar] [CrossRef] [PubMed]
- Arosio, P.; Elia, L.; Poli, M. Ferritin, cellular iron storage and regulation. IUBMB Life 2017, 69, 414–422. [Google Scholar] [CrossRef] [PubMed]
- Wang, Z.; Gao, H.; Zhang, Y.; Liu, G.; Niu, G.; Chen, X. Functional ferritin nanoparticles for biomedical applications. Front. Chem. Sci. Eng. 2017, 11, 633–646. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Corsi, B.; Cozzi, A.; Arosio, P.; Drysdale, J.; Santambrogio, P.; Campanella, A.; Biasiotto, G.; Albertini, A.; Levi, S. Human mitochondrial ferritin expressed in HeLa cells incorporates iron and affects cellular iron metabolism. J. Biol. Chem. 2002, 277, 22430–22437. [Google Scholar] [CrossRef] [PubMed]
- Waldo, G.S.; Wright, E.; Whang, Z.H.; Briat, J.F.; Theil, E.C.; Sayers, D.E. Formation of the ferritin iron mineral occurs in plastids. Plant Physiol. 1995, 109, 797–802. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Surguladze, N.; Thompson, K.M.; Beard, J.L.; Connor, J.R.; Fried, M.G. Interactions and Reactions of Ferritin with DNA. J. Biol. Chem. 2004, 279, 14694–14702. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Surguladze, N.; Patton, S.; Cozzi, A.; Fried, M.G.; Connor, J.R. Characterization of nuclear ferritin and mechanism of translocation. Biochem. J. 2005, 388, 731–740. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Alkhateeb, A.A.; Connor, J.R. Nuclear ferritin: A new role for ferritin in cell biology. Biochim. Biophys. Acta Gen. Subj. 2010, 1800, 793–797. [Google Scholar] [CrossRef] [PubMed]
- Knovich, M.A.; Storey, J.A.; Coffman, L.G.; Torti, S.V.; Torti, F.M. Ferritin for the clinician. Blood Rev. 2009, 23, 95–104. [Google Scholar] [CrossRef] [PubMed]
- Kuiper, M.A.; Mulder, C.; van Kamp, G.J.; Scheltens, P.; Wolters, E.C. Cerebrospinal fluid ferritin levels of patients with Parkinson’s disease, Alzheimer’s disease, and multiple system atrophy. J. Neural Transm. 1994, 7, 109–114. [Google Scholar] [CrossRef]
- Liu, X.; Madhankumar, A.B.; Slagle-Webb, B.; Sheehan, J.M.; Surguladze, N.; Connor, J.R. Heavy chain ferritin siRNA delivered by cationic liposomes increases sensitivity of cancer cells to chemotherapeutic agents. Cancer Res. 2011, 71, 2240–2249. [Google Scholar] [CrossRef] [PubMed]
- Yang, H.; Yang, M.; Guan, H.; Liu, Z.; Zhao, S.; Takeuchi, S.; Yanagisawa, D.; Tooyama, I. Mitochondrial ferritin in neurodegenerative diseases. Neurosci. Res. 2013, 77, 1–7. [Google Scholar] [CrossRef] [PubMed]
- Algarín, C.; Peirano, P.; Garrido, M.; Pizarro, F.; Lozoff, B. Iron Deficiency Anemia in Infancy: Long-Lasting Effects on Auditory and Visual System Functioning. Pediatr. Res. 2003, 53, 217–223. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Tomatsu, S.; Orii, K.O.; Fleming, R.E.; Holden, C.C.; Waheed, A.; Britton, R.S.; Gutierrez, M.A.; Velez-Castrillon, S.; Bacon, B.R.; Sly, W.S. Contribution of the H63D mutation in HFE to murine hereditary hemochromatosis. Proc. Natl. Acad. Sci. USA 2003, 100, 15788–15793. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Nixon, A.M.; Neely, E.; Simpson, I.A.; Connor, J.R. The role of HFE genotype in macrophage phenotype. J. Neuroinflamm. 2018, 15, 30. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Stephenson, E.; Nathoo, N.; Mahjoub, Y.; Dunn, J.F.; Yong, V.W. Iron in multiple sclerosis: Roles in neurodegeneration and repair. Nat. Rev. Neurol. 2014, 10, 459–468. [Google Scholar] [CrossRef] [PubMed]
- Peters, D.G.; Connor, J.R.; Meadowcroft, M.D. The relationship between iron dyshomeostasis and amyloidogenesis in Alzheimer’s disease: Two sides of the same coin. Neurobiol. Dis. 2015, 81, 49–65. [Google Scholar] [CrossRef] [PubMed]
- Biasiotto, G.; Di Lorenzo, D.; Archetti, S.; Zanella, I. Iron and Neurodegeneration: Is Ferritinophagy the Link? Mol. Neurobiol. 2016, 53, 5542–5574. [Google Scholar] [CrossRef] [PubMed]
- ten Kate, J.; Wolthuis, A.; Westerhuis, B.; van Deursen, C. The Iron Content of Serum Ferritin: Physiological Importance and Diagnostic Value. Clin. Chem. Lab. Med. 1997, 35, 53–56. [Google Scholar] [CrossRef] [Green Version]
- Hearnshaw, S.; Thompson, N.P.; Mcgill, A. The epidemiology of hyperferritinaemia. World J. Gastroenterol. 2006, 12, 5866–5869. [Google Scholar] [CrossRef] [PubMed]
- Cohen, L.A.; Gutierrez, L.; Weiss, A.; Leichtmann-Bardoogo, Y.; Zhang, D.L.; Crooks, D.R.; Sougrat, R.; Morgenstern, A.; Galy, B.; Hentze, M.W.; et al. Serum ferritin is derived primarily from macrophages through a nonclassical secretory pathway. Blood 2010, 116, 1574–1584. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Connor, J.R.; Zhang, X.; Nixon, A.M.; Webb, B.; Perno, J.R. Comparative evaluation of nephrotoxicity and management by macrophages of intravenous pharmaceutical iron formulations. PLoS ONE 2015, 10, e0125272. [Google Scholar] [CrossRef] [PubMed]
- Leimberg, M.J.; Prus, E.; Konijn, A.M.; Fibach, E. Macrophages function as a ferritin iron source for cultured human erythroid precursors. J. Cell. Biochem. 2008, 103, 1211–1218. [Google Scholar] [CrossRef] [PubMed]
- Kidane, T.Z.; Sauble, E.; Linder, M.C. Release of iron from ferritin requires lysosomal activity. Am. J. Physiol. Cell Physiol. 2006, 291, C445–C455. [Google Scholar] [CrossRef] [PubMed]
- Briley-Saebo, K.; Bjørnerud, A.; Grant, D.; Ahlstrom, H.; Berg, T.; Kindberg, G.M. Hepatic cellular distribution and degradation of iron oxide nanoparticles following single intravenous injection in rats: Implications for magnetic resonance imaging. Cell Tissue Res. 2004, 316, 315–323. [Google Scholar] [CrossRef] [PubMed]
- Blott, E.J.; Griffiths, G.M. Secretory lysosomes. Nat. Rev. Mol. Cell Biol. 2002, 3, 122–131. [Google Scholar] [CrossRef] [PubMed]
- Truman-Rosentsvit, M.; Berenbaum, D.; Spektor, L.; Cohen, L.A.; Belizowsky-Moshe, S.; Lifshitz, L.; Ma, J.; Li, W.; Kesselman, E.; Abutbul-Ionita, I.; et al. Ferritin is secreted via 2 distinct nonclassical vesicular pathways. Blood 2018, 131, 342–352. [Google Scholar] [CrossRef] [PubMed]
- Mrowczynski, O.D.; Madhankumar, A.B.; Slagle-Webb, B.; Lee, S.Y.; Zacharia, B.E.; Connor, J.R. HFE genotype affects exosome phenotype in cancer. Biochim. Biophys. Acta Gen. Subj. 2017, 1861, 1921–1928. [Google Scholar] [CrossRef] [PubMed]
- Kimura, T.; Jia, J.; Kumar, S.; Won Choi, S.; Gu, Y.; Mudd, M.; Dupont, N.; Jiang, S.; Peters, R.; Farzam, F.; et al. Dedicated SNAREs and specialized TRIM cargo receptors mediate secretory autophagy. EMBO J. 2017, 36, 42–60. [Google Scholar] [CrossRef] [PubMed]
- Fisher, J.; Devraj, K.; Ingram, J.; Slagle-Webb, B.; Madhankumar, A.B.; Liu, X.; Klinger, M.; Simpson, I.A.; Connor, J.R. Ferritin: A novel mechanism for delivery of iron to the brain and other organs. Am J. Physiol. Cell Physiol. 2007, 293, C641–C649. [Google Scholar] [CrossRef] [PubMed]
- Chiou, B.; Neal, E.H.; Bowman, A.B.; Lippmann, E.S.; Simpson, I.A.; Connor, J.R. Endothelial cells are critical regulators of iron transport in a model of the human blood–brain barrier. J. Cereb. Blood Flow Metab. 2018, in press. [Google Scholar] [CrossRef] [PubMed]
- Chiou, B.; Neal, E.H.; Bowman, A.B.; Lippmann, E.S.; Simpson, I.A.; Connor, J.R. Pharmaceutical iron formulations do not cross a model of the human blood-brain barrier. PLoS ONE 2018, 13, e0198775. [Google Scholar] [CrossRef] [PubMed]
- Simpson, I.A.; Ponnuru, P.; Klinger, M.E.; Myers, R.L.; Devraj, K.; Coe, C.L.; Lubach, G.R.; Carruthers, A.; Connor, J.R. A Novel Model for Brain Iron Uptake: Introducing the Concept of Regulation. J. Cereb. Blood Flow Metab. 2015, 35, 48–57. [Google Scholar] [CrossRef] [PubMed]
- Duck, K.A.; Connor, J.R. Iron uptake and transport across physiological barriers. BioMetals 2016, 29, 573–591. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Duck, K.A.; Simpson, I.A.; Connor, J.R. Regulatory mechanisms for iron transport across the blood-brain barrier. Biochem. Biophys. Res. Commun. 2017, 494, 70–75. [Google Scholar] [CrossRef] [PubMed]
- Todorich, B.; Zhang, X.; Connor, J.R. H-ferritin is the major source of iron for oligodendrocytes. Glia 2011, 59, 927–935. [Google Scholar] [CrossRef] [PubMed]
- Adams, P.C.; Chau, L.A. Uptake of ferritin by isolated rat hepatocytes. Effect of metabolic inhibitors and iron. Clin. Investig. Med. Médecine Clin. Exp. 1993, 16, 15–21. [Google Scholar]
- Blight, G.D.; Morgan, E.H. Ferritin and iron uptake by reticulocytes. Br. J. Haematol. 1983, 55, 59–71. [Google Scholar] [CrossRef] [PubMed]
- Moss, D.; Powell, L.W.; Arosio, P.; Halliday, J.W. Characterization of the ferritin receptors of human T lymphoid (MOLT-4) cells. J. Lab. Clin. Med. 1992, 119, 273–279. [Google Scholar] [PubMed]
- Sakamoto, S.; Kawabata, H.; Masuda, T.; Uchiyama, T.; Mizumoto, C.; Ohmori, K.; Koeffler, H.P.; Kadowaki, N.; Takaori-Kondo, A. H-Ferritin is Preferentially Incorporated by Human Erythroid Cells through Transferrin Receptor 1 in a Threshold-Dependent Manner. PLoS ONE 2015, 10, e0139915. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Gelvan, D.; Fibach, E.; Meyron-Holtz, E.G.; Konijn, A.M. Ferritin uptake by human erythroid precursors is a regulated iron uptake pathway. Blood 1996, 88, 3200–3207. [Google Scholar] [PubMed]
- Beard, J.L.; Connor, J.R. Iron status and neural functioning. Annu. Rev. Nutr. 2003, 23, 41–58. [Google Scholar] [CrossRef] [PubMed]
- Hulet, S.; Heyliger, S.; Powers, S.; Connor, J. Oligodendrocyte progenitor cells internalize ferritin via clathrin-dependent receptor mediated endocytosis. J. Neurosci. Res. 2000, 61, 52–60. [Google Scholar] [CrossRef]
- Li, J.Y.; Paragas, N.; Ned, R.M.; Qiu, A.; Viltard, M.; Leete, T.; Drexler, I.R.; Chen, X.; Sanna-Cherchi, S.; Mohammed, F.; et al. Scara5 is a Ferritin Receptor Mediating Non-Transferrin Iron Delivery. Dev. Cell 2009, 16, 35–46. [Google Scholar] [CrossRef] [PubMed]
- Chen, T.T.; Li, L.; Chung, D.H.; Allen, C.D.C.; Torti, S.V.; Torti, F.M.; Cyster, J.G.; Chen, C.Y.; Brodsky, F.M.; Niemi, E.C.; et al. TIM-2 is expressed on B cells and in liver and kidney and is a receptor for H-ferritin endocytosis. J. Exp. Med. 2005, 202, 955–965. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Todorich, B.; Zhang, X.; Slagle-Webb, B.; Seaman, W.E.; Connor, J.R. Tim-2 is the receptor for H-ferritin on oligodendrocytes. J. Neurochem. 2008, 107, 1495–1505. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Han, J.; Seaman, W.E.; Di, X.; Wang, W.; Willingham, M.; Torti, F.M.; Torti, S.V. Iron uptake mediated by binding of H-ferritin to the TIM-2 receptor in mouse cells. PLoS ONE 2011, 6, e23800. [Google Scholar] [CrossRef] [PubMed]
- Chiou, B.; Lucassen, E.; Sather, M.; Kallianpur, A.; Connor, J. Semaphorin4A and H-ferritin utilize Tim-1 on human oligodendrocytes: A novel neuro-immune axis. Glia 2018, 66, 1317–1330. [Google Scholar] [CrossRef] [PubMed]
- Li, R.; Luo, C.; Mines, M.; Zhang, J.; Fan, G.H. Chemokine CXCL12 Induces Binding of Ferritin Heavy Chain to the Chemokine Receptor CXCR4, Alters CXCR4 Signaling, and Induces Phosphorylation and Nuclear Translocation of Ferritin Heavy Chain. J. Biol. Chem. 2006, 281, 37616–37627. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Li, L.; Fang, C.J.; Ryan, J.C.; Niemi, E.C.; Lebrón, J.A.; Björkman, P.J.; Arase, H.; Torti, F.M.; Torti, S.V.; Nakamura, M.C.; et al. Binding and uptake of H-ferritin are mediated by human transferrin receptor-1. Proc. Natl. Acad. Sci. USA 2010, 107, 3505–3510. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hulet, S.; Powers, S.; Connor, J. Distribution of transferrin and ferritin binding in normal and multiple sclerotic human brains. J. Neurol. Sci. 1999, 165, 48–55. [Google Scholar] [CrossRef]
- Akinc, A.; Battaglia, G. Exploiting Endocytosis for Nanomedicines. Cold Spring Harb. Perspect. Biol. 2013, 5, a016980. [Google Scholar] [CrossRef] [PubMed]
- Das, A.; Nag, S.; Mason, A.B.; Barroso, M.M. Endosome–mitochondria interactions are modulated by iron release from transferrin. J. Cell Biol. 2016, 214, 831–845. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Mancias, J.D.; Wang, X.; Gygi, S.P.; Harper, J.W.; Kimmelman, A.C. Quantitative proteomics identifies NCOA4 as the cargo receptor mediating ferritinophagy. Nature 2014, 509, 105–109. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Mancias, J.D.; Vaites, L.P.; Nissim, S.; Biancur, D.E.; Kim, A.J.; Wang, X.; Liu, Y.; Goessling, W.; Kimmelman, A.C.; Harper, J.W. Ferritinophagy via NCOA4 is required for erythropoiesis and is regulated by iron dependent HERC2-mediated proteolysis. Elife 2015, 4, e10308. [Google Scholar] [CrossRef] [PubMed]
- Mehlhase, J.; Sandig, G.; Pantopoulos, K.; Grune, T. Oxidation-induced ferritin turnover in microglial cells: Role of proteasome. Free Radic. Biol. Med. 2005, 38, 276–285. [Google Scholar] [CrossRef] [PubMed]
- Linder, M.C. Mobilization of stored iron in mammals: A review. Nutrients 2013, 5, 4022–4050. [Google Scholar] [CrossRef] [PubMed]
- Zhang, Y.; Mikhael, M.; Xu, D.; Li, Y.; Soe-Lin, S.; Ning, B.; Li, W.; Nie, G.; Zhao, Y.; Ponka, P. Lysosomal Proteolysis Is the Primary Degradation Pathway for Cytosolic Ferritin and Cytosolic Ferritin Degradation Is Necessary for Iron Exit. Antioxid. Redox Signal. 2010, 13, 999–1009. [Google Scholar] [CrossRef] [PubMed]
- Kim, M.; Rho, Y.; Jin, K.S.; Ahn, B.; Jung, S.; Kim, H.; Ree, M. pH-Dependent Structures of Ferritin and Apoferritin in Solution: Disassembly and Reassembly. Biomacromolecules 2011, 12, 1629–1640. [Google Scholar] [CrossRef] [PubMed]
- Ghinea, N.; Hasu, M. Charge effect on binding, uptake and transport of ferritin through fenestrated endothelium. J. Submicrosc. Cytol. 1986, 18, 647–659. [Google Scholar] [PubMed]
- Mazzucchelli, S.; Truffi, M.; Baccarini, F.; Beretta, M.; Sorrentino, L.; Bellini, M.; Rizzuto, M.A.; Ottria, R.; Ravelli, A.; Ciuffreda, P.; et al. H-Ferritin-nanocaged olaparib: A promising choice for both BRCA-mutated and sporadic triple negative breast cancer. Sci. Rep. 2017, 7, 7505. [Google Scholar] [CrossRef] [PubMed]
- Mazzucchelli, S.; Bellini, M.; Fiandra, L.; Truffi, M.; Rizzuto, M.A.; Sorrentino, L.; Longhi, E.; Nebuloni, M.; Prosperi, D.; Corsi, F. Nanometronomic treatment of 4T1 breast cancer with nanocaged doxorubicin prevents drug resistance and circumvents cardiotoxicity. Oncotarget 2016, 8, 8383–8396. [Google Scholar] [CrossRef] [PubMed]
- Liang, M.; Fan, K.; Zhou, M.; Duan, D.; Zheng, J.; Yang, D.; Feng, J.; Yan, X. H-ferritin-nanocaged doxorubicin nanoparticles specifically target and kill tumors with a single-dose injection. Proc. Natl. Acad. Sci. USA 2014, 111, 14900–14905. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kwon, C.; Kang, Y.J.; Jeon, S.; Jung, S.; Hong, S.Y.; Kang, S. Development of Protein-Cage-Based Delivery Nanoplatforms by Polyvalently Displaying β-Cyclodextrins on the Surface of Ferritins Through Copper(I)-Catalyzed Azide/Alkyne Cycloaddition. Macromol. Biosci. 2012, 12, 1452–1458. [Google Scholar] [CrossRef] [PubMed]
- Luo, Y.; Wang, X.; Du, D.; Lin, Y. Hyaluronic acid-conjugated apoferritin nanocages for lung cancer targeted drug delivery. Biomater. Sci. 2015, 3, 1386–1394. [Google Scholar] [CrossRef] [PubMed]
- Truffi, M.; Fiandra, L.; Sorrentino, L.; Monieri, M.; Corsi, F.; Mazzucchelli, S. Ferritin nanocages: A biological platform for drug delivery, imaging and theranostics in cancer. Pharmacol. Res. 2016, 107, 57–65. [Google Scholar] [CrossRef] [PubMed]
- Li, L.; Muñoz-Culla, M.; Carmona, U.; Lopez, M.P.; Yang, F.; Trigueros, C.; Otaegui, D.; Zhang, L.; Knez, M. Ferritin-mediated siRNA delivery and gene silencing in human tumor and primary cells. Biomaterials 2016, 98, 143–151. [Google Scholar] [CrossRef] [PubMed]
- Li, X.; Qiu, L.; Zhu, P.; Tao, X.; Imanaka, T.; Zhao, J.; Huang, Y.; Tu, Y.; Cao, X. Epidermal Growth Factor-Ferritin H-Chain Protein Nanoparticles for Tumor Active Targeting. Small 2012, 8, 2505–2514. [Google Scholar] [CrossRef] [PubMed]
- Conti, L.; Lanzardo, S.; Ruiu, R.; Cadenazzi, M.; Cavallo, F.; Aime, S.; Crich, S.G. L-Ferritin targets breast cancer stem cells and delivers therapeutic and imaging agents. Oncotarget 2016, 7, 66713–66727. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Alkhateeb, A.A.; Han, B.; Connor, J.R. Ferritin stimulates breast cancer cells through an iron-independent mechanism and is localized within tumor-associated macrophages. Breast Cancer Res. Treat. 2013, 137, 733–744. [Google Scholar] [CrossRef] [PubMed]
- Uchida, M.; Flenniken, M.L.; Allen, M.; Willits, D.A.; Crowley, B.E.; Brumfield, S.; Willis, A.F.; Jackiw, L.; Jutila, M.; Young, M.J.; et al. Targeting of cancer cells with ferrimagnetic ferritin cage nanoparticles. J. Am. Chem. Soc. 2006, 128, 16626–16633. [Google Scholar] [CrossRef] [PubMed]
- Chen, Z.; Zhai, M.; Xie, X.; Zhang, Y.; Ma, S.; Li, Z.; Yu, F.; Zhao, B.; Zhang, M.; Yang, Y.; et al. Apoferritin Nanocage for Brain Targeted Doxorubicin Delivery. Mol. Pharm. 2017, 14, 3087–3097. [Google Scholar] [CrossRef] [PubMed]
- Wu, T.; Li, Y.; Liu, B.; Zhang, S.; Wu, L.; Zhu, X.; Chen, Q. Expression of Ferritin Light Chain (FTL) is Elevated in Glioblastoma, and FTL Silencing Inhibits Glioblastoma Cell Proliferation via the GADD45/JNK Pathway. PLoS ONE 2016, 11, e0149361. [Google Scholar] [CrossRef] [PubMed]
- Kanekiyo, M.; Wei, C.J.; Yassine, H.M.; McTamney, P.M.; Boyington, J.C.; Whittle, J.R.R.; Rao, S.S.; Kong, W.P.; Wang, L.; Nabel, G.J. Self-assembling influenza nanoparticle vaccines elicit broadly neutralizing H1N1 antibodies. Nature 2013, 499, 102–106. [Google Scholar] [CrossRef] [PubMed]
- Kanekiyo, M.; Bu, W.; Joyce, M.G.; Meng, G.; Whittle, J.R.R.; Baxa, U.; Yamamoto, T.; Narpala, S.; Todd, J.-P.; Rao, S.S.; et al. Rational Design of an Epstein-Barr Virus Vaccine Targeting the Receptor-Binding Site. Cell 2015, 162, 1090–1100. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Han, J.-A.; Kang, Y.J.; Shin, C.; Ra, J.S.; Shin, H.H.; Hong, S.Y.; Do, Y.; Kang, S. Ferritin protein cage nanoparticles as versatile antigen delivery nanoplatforms for dendritic cell (DC)-based vaccine development. Nanomedicine 2014, 10, 561–569. [Google Scholar] [CrossRef] [PubMed]
- Puttick, S.; Bell, C.; Dowson, N.; Rose, S.; Fay, M. PET, MRI, and simultaneous PET/MRI in the development of diagnostic and therapeutic strategies for glioma. Drug Discov. Today 2015, 20, 306–317. [Google Scholar] [CrossRef] [PubMed]
- Dubois, J.; Dehaene-Lambertz, G.; Kulikova, S.; Poupon, C.; Hüppi, P.S.; Hertz-Pannier, L. The early development of brain white matter: A review of imaging studies in fetuses, newborns and infants. Neuroscience 2014, 276, 48–71. [Google Scholar] [CrossRef] [PubMed]
- Benders, M.J.N.L.; Kersbergen, K.J.; de Vries, L.S. Neuroimaging of White Matter Injury, Intraventricular and Cerebellar Hemorrhage. Clin. Perinatol. 2014, 41, 69–82. [Google Scholar] [CrossRef] [PubMed]
- Essig, M.; Shiroishi, M.S.; Nguyen, T.B.; Saake, M.; Provenzale, J.M.; Enterline, D.; Anzalone, N.; Dörfler, A.; Rovira, À.; Wintermark, M.; et al. Perfusion MRI: The Five Most Frequently Asked Technical Questions. Am. J. Roentgenol. 2013, 200, 24–34. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Bhogal, P.; Uff, C.; Makalanda, H.L.D. Vessel wall MRI and intracranial aneurysms. J. Neurointerv. Surg. 2016, 8, 1160–1162. [Google Scholar] [CrossRef] [PubMed]
- He, D.; Marles-Wright, J. Ferritin family proteins and their use in bionanotechnology. New Biotechnol. 2015, 32, 651–657. [Google Scholar] [CrossRef] [PubMed]
- Cutrin, J.C.; Crich, S.G.; Burghelea, D.; Dastrù, W.; Aime, S. Curcumin/Gd Loaded Apoferritin: A Novel “Theranostic” Agent To Prevent Hepatocellular Damage in Toxic Induced Acute Hepatitis. Mol. Pharm. 2013, 10, 2079–2085. [Google Scholar] [CrossRef] [PubMed]
- Geninatti Crich, S.; Cadenazzi, M.; Lanzardo, S.; Conti, L.; Ruiu, R.; Alberti, D.; Cavallo, F.; Cutrin, J.C.; Aime, S. Targeting ferritin receptors for the selective delivery of imaging and therapeutic agents to breast cancer cells. Nanoscale 2015, 7, 6527–6533. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Sevcenco, A.-M.; Paravidino, M.; Vrouwenvelder, J.S.; Wolterbeek, H.T.; van Loosdrecht, M.C.M.; Hagen, W.R. Phosphate and arsenate removal efficiency by thermostable ferritin enzyme from Pyrococcus furiosus using radioisotopes. Water Res. 2015, 76, 181–186. [Google Scholar] [CrossRef] [PubMed]
- Muckenthaler, M.U.; Galy, B.; Hentze, M.W. Systemic Iron Homeostasis and the Iron-Responsive Element/Iron-Regulatory Protein (IRE/IRP) Regulatory Network. Annu. Rev. Nutr. 2008, 28, 197–213. [Google Scholar] [CrossRef] [PubMed]
- Kwak, E.L.; Larochelle, D.A.; Beaumont, C.; Torti, S.V.; Torti, F.M. Role for NF-κB in the Regulation of Ferritin H by Tumor Necrosis Factor-α. J. Biol. Chem. 1995, 270, 15285–15293. [Google Scholar] [CrossRef] [PubMed]
- Peyssonnaux, C.; Zinkernagel, A.S.; Schuepbach, R.A.; Rankin, E.; Vaulont, S.; Haase, V.H.; Nizet, V.; Johnson, R.S. Regulation of iron homeostasis by the hypoxia-inducible transcription factors (HIFs). J. Clin. Investig. 2007, 117, 1926–1932. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hoesel, B.; Schmid, J.A. The complexity of NF-κB signaling in inflammation and cancer. Mol. Cancer 2013, 12, 86. [Google Scholar] [CrossRef] [PubMed]
- Xue, Y.; Yun, D.; Esmon, A.; Zou, P.; Zuo, S.; Yu, Y.; He, F.; Yang, P.; Chen, X. Proteomic Dissection of Agonist-Specific TLR-Mediated Inflammatory Responses on Macrophages at Subcellular Resolution. J. Proteome Res. 2008, 7, 3180–3193. [Google Scholar] [CrossRef] [PubMed]
- Miller, L.L.; Miller, S.C.; Torti, S.V.; Tsuji, Y.; Torti, F.M. Iron-independent induction of ferritin H chain by tumor necrosis factor. Proc. Natl. Acad. Sci. USA 1991, 88, 4946–4950. [Google Scholar] [CrossRef] [PubMed]
- Lissoni, P.; Cazzaniga, M.; Ardizzoia, A.; Rossini, F.; Fiorelli, G.; Tancini, G.; Pittalis, S.; Barni, S. Cytokine regulation of iron metabolism: Effect of low-dose interleukin-2 subcutaneous therapy on ferritin, transferrin and iron blood concentrations in cancer patients. J. Biol. Regul. Homeost. Agents 1993, 7, 31–33. [Google Scholar] [PubMed]
- Gray, C.P.; Franco, A.V.; Arosio, P.; Hersey, P. Immunosuppressive effects of melanoma-derived heavy-chain ferritin are dependent on stimulation of IL-10 production. Int. J. Cancer 2001, 92, 843–850. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Dignass, A.; Farrag, K.; Stein, J. Limitations of Serum Ferritin in Diagnosing Iron Deficiency in Inflammatory Conditions. Int. J. Chronic Dis. 2018, 2018, 9394060. [Google Scholar] [CrossRef] [PubMed]
- Ruscitti, P.; Cipriani, P.; Di Benedetto, P.; Liakouli, V.; Berardicurti, O.; Carubbi, F.; Ciccia, F.; Guggino, G.; Triolo, G.; Giacomelli, R. H-ferritin and proinflammatory cytokines are increased in the bone marrow of patients affected by macrophage activation syndrome. Clin. Exp. Immunol. 2018, 191, 220–228. [Google Scholar] [CrossRef] [PubMed]
- Kell, D.B.; Pretorius, E. Serum ferritin is an important inflammatory disease marker, as it is mainly a leakage product from damaged cells. Metallomics 2014, 6, 748. [Google Scholar] [CrossRef] [PubMed]
- Gomes, A.; Moreira, A.; Mesquita, G.; Gomes, M. Modulation of Iron Metabolism in Response to Infection: Twists for All Tastes. Pharmaceuticals 2018, 11, 84. [Google Scholar] [CrossRef] [PubMed]
- Fan, Y.; Zhang, J.; Cai, L.; Wang, S.; Liu, C.; Zhang, Y.; You, L.; Fu, Y.; Shi, Z.; Yin, Z.; et al. The effect of anti-inflammatory properties of ferritin light chain on lipopolysaccharide-induced inflammatory response in murine macrophages. Biochim. Biophys. Acta Mol. Cell Res. 2014, 1843, 2775–2783. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Parthasarathy, N.; Torti, S.V.; Torti, F.M. Ferritin binds to light chain of human H-kininogen and inhibits kallikrein-mediated bradykinin release. Biochem. J. 2002, 365, 279–286. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Cohen-Solal, A.; Leclercq, C.; Deray, G.; Lasocki, S.; Zambrowski, J.J.; Mebazaa, A.; de Groote, P.; Damy, T.; Galinier, M. Iron deficiency: an emerging therapeutic target in heart failure. Heart 2014, 100, 1414–1420. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wang, W.; Knovich, M.A.; Coffman, L.G.; Torti, F.M.; Torti, S. V Serum ferritin: Past, present and future. Biochim. Biophys. Acta 2010, 1800, 760–769. [Google Scholar] [CrossRef] [PubMed]
- Ueda, N.; Takasawa, K. Impact of Inflammation on Ferritin, Hepcidin and the Management of Iron Deficiency Anemia in Chronic Kidney Disease. Nutrients 2018, 10, 1173. [Google Scholar] [CrossRef] [PubMed]
- Recalcati, S.; Invernizzi, P.; Arosio, P.; Cairo, G. New functions for an iron storage protein: The role of ferritin in immunity and autoimmunity. J. Autoimmun. 2008, 30, 84–89. [Google Scholar] [CrossRef] [PubMed]
- Gozzelino, R.; Andrade, B.B.; Larsen, R.; Luz, N.F.; Vanoaica, L.; Seixas, E.; Coutinho, A.; Cardoso, S.; Rebelo, S.; Poli, M.; et al. Metabolic Adaptation to Tissue Iron Overload Confers Tolerance to Malaria. Cell Host Microbe 2012, 12, 693–704. [Google Scholar] [CrossRef] [PubMed]
- Weis, S.; Carlos, A.R.; Moita, M.R.; Singh, S.; Blankenhaus, B.; Cardoso, S.; Larsen, R.; Rebelo, S.; Schäuble, S.; Del Barrio, L.; et al. Metabolic Adaptation Establishes Disease Tolerance to Sepsis. Cell 2017, 169, 1263–1275. [Google Scholar] [CrossRef] [PubMed]
- Reddy, V.P.; Chinta, K.C.; Saini, V.; Glasgow, J.N.; Hull, T.D.; Traylor, A.; Rey-Stolle, F.; Soares, M.P.; Madansein, R.; Rahman, M.A.; et al. Ferritin H Deficiency in Myeloid Compartments Dysregulates Host Energy Metabolism and Increases Susceptibility to Mycobacterium tuberculosis Infection. Front. Immunol. 2018, 9, 860. [Google Scholar] [CrossRef] [PubMed]
- Torti, S.V.; Torti, F.M. Human H-kininogen is a ferritin-binding protein. J. Biol. Chem. 1998, 273, 13630–13635. [Google Scholar] [CrossRef] [PubMed]
- Kaplan, A.P. The Bradykinin-Forming Cascade: A Historical Perspective. In Chemical Immunology and Allergy; Karger: Basel, Switzerland, 2014; Volume 100, pp. 205–213. [Google Scholar]
- Barnes, P.J. Bradykinin and asthma. Thorax 1992, 47, 979–983. [Google Scholar] [CrossRef] [PubMed]
- Stadnicki, A. Intestinal tissue kallikrein-kinin system in inflammatory bowel disease. Inflamm. Bowel Dis. 2011, 17, 645–654. [Google Scholar] [CrossRef] [PubMed]
- Sharma, J.N. Involvement of the kinin-forming system in the physiopathology of rheumatoid inflammation. Agents Actions 1992, 38, 343–361. [Google Scholar] [PubMed]
- Sharma, J.N.; Buchanan, W.W. Pathogenic responses of bradykinin system in chronic inflammatory rheumatoid disease. Exp. Toxicol. Pathol. 1994, 46, 421–433. [Google Scholar] [CrossRef]
- Cook, C.I.; Yu, B.P. Iron accumulation in aging: Modulation by dietary restriction. Mech. Ageing Dev. 1998, 102, 1–13. [Google Scholar] [CrossRef]
- Hagemeier, J.; Geurts, J.J.; Zivadinov, R. Brain iron accumulation in aging and neurodegenerative disorders. Expert Rev. Neurother. 2012, 12, 1467–1480. [Google Scholar] [CrossRef] [PubMed]
- Pirpamer, L.; Hofer, E.; Gesierich, B.; De Guio, F.; Freudenberger, P.; Seiler, S.; Duering, M.; Jouvent, E.; Duchesnay, E.; Dichgans, M.; et al. Determinants of iron accumulation in the normal aging brain. Neurobiol. Aging 2016, 43, 149–155. [Google Scholar] [CrossRef] [PubMed]
- Connor, J.R.; Snyder, B.S.; Arosio, P.; Loeffler, D.A.; LeWitt, P. A Quantitative Analysis of Isoferritins in Select Regions of Aged, Parkinsonian, and Alzheimer’s Diseased Brains. J. Neurochem. 1995, 65, 717–724. [Google Scholar] [CrossRef] [PubMed]
- Fonseca-Nunes, A.; Jakszyn, P.; Agudo, A. Iron and Cancer Risk-A Systematic Review and Meta-analysis of the Epidemiological Evidence. Cancer Epidemiol. Biomarkers Prev. 2014, 23, 12–31. [Google Scholar] [CrossRef] [PubMed]
- Alkhateeb, A.A.; Connor, J.R. The significance of ferritin in cancer: Anti-oxidation, inflammation and tumorigenesis. Biochim. Biophys. Acta Rev. Cancer 2013, 1836, 245–254. [Google Scholar] [CrossRef] [PubMed]
- Alsina, D.; Purroy, R.; Ros, J.; Tamarit, J. Iron in Friedreich Ataxia: A Central Role in the Pathophysiology or an Epiphenomenon? Pharmaceuticals 2018, 11, 89. [Google Scholar] [CrossRef] [PubMed]
- Levi, S.; Rovida, E. Neuroferritinopathy: From ferritin structure modification to pathogenetic mechanism. Neurobiol. Dis. 2015, 81, 134–143. [Google Scholar] [CrossRef] [PubMed]
- Barbeito, A.G.; Levade, T.; Delisle, M.B.; Ghetti, B.; Vidal, R. Abnormal iron metabolism in fibroblasts from a patient with the neurodegenerative disease hereditary ferritinopathy. Mol. Neurodegener. 2010, 5, 50. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Maccarinelli, F.; Pagani, A.; Cozzi, A.; Codazzi, F.; Di Giacomo, G.; Capoccia, S.; Rapino, S.; Finazzi, D.; Politi, L.S.; Cirulli, F.; et al. A novel neuroferritinopathy mouse model (FTL 498InsTC) shows progressive brain iron dysregulation, morphological signs of early neurodegeneration and motor coordination deficits. Neurobiol. Dis. 2015, 81, 119–133. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Riederer, P.; Sofic, E.; Rausch, W.D.; Schmidt, B.; Reynolds, G.P.; Jellinger, K.; Youdim, M.B.H. Transition Metals, Ferritin, Glutathione, and Ascorbic Acid in Parkinsonian Brains. J. Neurochem. 1989, 52, 515–520. [Google Scholar] [CrossRef] [PubMed]
- Dexter, D.T.; Carayon, A.; Vidailhet, M.; Ruberg, M.; Agid, F.; Agid, Y.; Lees, A.J.; Wells, F.R.; Jenner, P.; Marsden, C.D. Decreased Ferritin Levels in Brain in Parkinson’s Disease. J. Neurochem. 1990, 55, 16–20. [Google Scholar] [CrossRef] [PubMed]
- Thompson, K.; Menzies, S.; Muckenthaler, M.; Torti, F.M.; Wood, T.; Torti, S.V.; Hentze, M.W.; Beard, J.; Connor, J. Mouse brains deficient in H-ferritin have normal iron concentration but a protein profile of iron deficiency and increased evidence of oxidative stress. J. Neurosci. Res. 2003, 71, 46–63. [Google Scholar] [CrossRef] [PubMed]
- Hemmati-Dinarvand, M.; Taher-Aghdam, A.A.; Mota, A.; Zununi Vahed, S.; Samadi, N. Dysregulation of serum NADPH oxidase1 and ferritin levels provides insights into diagnosis of Parkinson’s disease. Clin. Biochem. 2017, 50, 1087–1092. [Google Scholar] [CrossRef] [PubMed]
- Kozina, E.; Sadasivan, S.; Jiao, Y.; Dou, Y.; Ma, Z.; Tan, H.; Kodali, K.; Shaw, T.; Peng, J.; Smeyne, R.J. Mutant LRRK2 mediates peripheral and central immune responses leading to neurodegeneration in vivo. Brain 2018, 141, 1753–1769. [Google Scholar] [CrossRef] [PubMed]
- Connor, J.R.; Patton, S.M.; Oexle, K.; Allen, R.P. Iron and restless legs syndrome: Treatment, genetics and pathophysiology. Sleep Med. 2017, 31, 61–70. [Google Scholar] [CrossRef] [PubMed]
- Allen, R.P.; Auerbach, S.; Bahrain, H.; Auerbach, M.; Earley, C.J. The prevalence and impact of restless legs syndrome on patients with iron deficiency anemia. Am. J. Hematol. 2013, 88, 261–264. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Akyol, A.; Kiylioglu, N.; Kadikoylu, G.; Bolaman, A.Z.; Ozgel, N. Iron deficiency anemia and restless legs syndrome: Is there an electrophysiological abnormality? Clin. Neurol. Neurosurg. 2003, 106, 23–27. [Google Scholar] [CrossRef] [PubMed]
- Connor, J.R.; Ponnuru, P.; Wang, X.-S.; Patton, S.M.; Allen, R.P.; Earley, C.J.; Leader, G.M. Profile of altered brain iron acquisition in restless legs syndrome. Brain 2011, 134, 959–968. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Connor, J.R.; Boyer, P.J.; Menzies, S.L.; Dellinger, B.; Allen, R.P.; Ondo, W.G.; Earley, C.J. Neuropathological examination suggests impaired brain iron acquisition in restless legs syndrome. Neurology 2003, 61, 304–309. [Google Scholar] [CrossRef] [PubMed]
- Lammers, N.; Curry-Hyde, A.; Smith, A.J.; Eastwood, P.R.; Straker, L.M.; Champion, D.; McArdle, N. Are serum ferritin and transferrin saturation risk markers for restless legs syndrome in young adults? Longitudinal and cross-sectional data from the Western Australian Pregnancy Cohort (Raine) Study. J. Sleep Res. 2018, e12741. [Google Scholar] [CrossRef] [PubMed]
- Zheng, Y.; Gao, L.; Wang, D.; Zang, D. Elevated levels of ferritin in the cerebrospinal fluid of amyotrophic lateral sclerosis patients. Acta Neurol. Scand. 2017, 136, 145–150. [Google Scholar] [CrossRef] [PubMed]
- Su, X.W.; Clardy, S.L.; Stephens, H.E.; Simmons, Z.; Connor, J.R. Serum ferritin is elevated in amyotrophic lateral sclerosis patients. Amyotroph. Lateral Scler. Front. Degener. 2015, 16, 102–107. [Google Scholar] [CrossRef] [PubMed]
- Nadjar, Y.; Gordon, P.; Corcia, P.; Bensimon, G.; Pieroni, L.; Meininger, V.; Salachas, F. Elevated Serum Ferritin Is Associated with Reduced Survival in Amyotrophic Lateral Sclerosis. PLoS ONE 2012, 7, e45034. [Google Scholar] [CrossRef] [PubMed]
- Yu, J.; Wang, N.; Qi, F.; Wang, X.; Zhu, Q.; Lu, Y.; Zhang, H.; Che, F.; Li, W. Serum ferritin is a candidate biomarker of disease aggravation in amyotrophic lateral sclerosis. Biomed. Rep. 2018, 9, 333–338. [Google Scholar] [CrossRef] [PubMed]
- Hu, X.; Yang, Y.; Su, J.; Yao, C. Meta-analysis of the relationship between amyotrophic lateral sclerosis and susceptibility to serum ferritin level elevation. Neurosciences 2016, 21, 120–125. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Li, W.; Garringer, H.J.; Goodwin, C.B.; Richine, B.; Acton, A.; VanDuyn, N.; Muhoberac, B.B.; Irimia-Dominguez, J.; Chan, R.J.; Peacock, M.; et al. Systemic and cerebral iron homeostasis in ferritin knock-out Mice. PLoS ONE 2015, 10, e0117435. [Google Scholar] [CrossRef] [PubMed] [Green Version]
© 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Share and Cite
Chiou, B.; Connor, J.R. Emerging and Dynamic Biomedical Uses of Ferritin. Pharmaceuticals 2018, 11, 124. https://doi.org/10.3390/ph11040124
Chiou B, Connor JR. Emerging and Dynamic Biomedical Uses of Ferritin. Pharmaceuticals. 2018; 11(4):124. https://doi.org/10.3390/ph11040124
Chicago/Turabian StyleChiou, Brian, and James R. Connor. 2018. "Emerging and Dynamic Biomedical Uses of Ferritin" Pharmaceuticals 11, no. 4: 124. https://doi.org/10.3390/ph11040124