A novel model for brain iron uptake: Introducing the concept of regulation

Journal of Cerebral Blood Flow and Metabolism

Volumn 35, Issue 1, 2015, Pages 48-57

  Simpson, Ian A ^a   Ponnuru, Padmavathi ^a   Klinger, Marianne E ^a   Myers, Roland L ^a   Devraj, Kavi ^a   Coe, Christopher L ^b   Lubach, Gabriele R ^b   Carruthers, Anthony ^c   Connor, James R ^a  

^a PENN STATE MILTON S HERSHEY MEDICAL CENTER   (United States)

^b UNIVERSITY OF WISCONSIN MADISON   (United States)

^c UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL   (United States)

Author keywords

blood brain barrier; mathematical modeling; neurochemistry; neurovascular coupling; neurovascular unit; receptors

Indexed keywords

APOTRANSFERRIN; HEPCIDIN; APOPROTEIN; IRON; TRANSFERRIN; TRANSFERRIN RECEPTOR;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; ASTROCYTE CULTURE; BLOOD BRAIN BARRIER; BRAIN METABOLISM; CEREBROSPINAL FLUID; CONTROLLED STUDY; IRON METABOLISM; IRON TRANSPORT; MALE; METABOLIC REGULATION; NONHUMAN; PRIMATE; RAT; ANIMAL; ASTROCYTE; BIOLOGICAL MODEL; BOVINE; BRAIN; CELL CULTURE; ENDOTHELIUM CELL; FEMALE; GENETICS; HETEROZYGOTE; HOMOZYGOTE; IRON DEFICIENCY ANEMIA; METABOLISM; MICROVASCULATURE; RHESUS MONKEY; SPRAGUE DAWLEY RAT; TRANSPORT AT THE CELLULAR LEVEL; VASCULARIZATION;

ANEMIA, IRON-DEFICIENCY; ANIMALS; APOPROTEINS; ASTROCYTES; BIOLOGICAL TRANSPORT; BLOOD-BRAIN BARRIER; BRAIN; CATTLE; CELLS, CULTURED; ENDOTHELIAL CELLS; FEMALE; HEPCIDINS; HETEROZYGOTE; HOMOZYGOTE; IRON; MACACA MULATTA; MALE; MICROVESSELS; MODELS, BIOLOGICAL; RATS, SPRAGUE-DAWLEY; RECEPTORS, TRANSFERRIN; TRANSFERRIN;

EID: 84920646171     PISSN: 0271678X     EISSN: 15597016     Source Type: Journal    
DOI: 10.1038/jcbfm.2014.168     Document Type: Article

References (40)

1. Zecca L, Youdim MB, Riederer P, Connor JR, Crichton RR. Iron, brain ageing and neurodegenerative disorders. Nat Rev Neurosci 2004; 5: 863-873.
2. Lozoff B, Beard J, Connor J, Barbara F, Georgieff M, Schallert T. Long-lasting neural and behavioral effects of iron deficiency in infancy. Nutr Rev 2006; 64: S34-S43, discussion S72-91.
3. Beard JL, Connor JR. Iron status and neural functioning. Ann Rev Nutr 2003; 23: 41-58.
4. Unger EL, Earley CJ, Beard JL. Diurnal cycle influences peripheral and brain iron levels in mice. J Appl Physiol (1985) 2009; 106: 187-193.
5. Klausner RD, Van Renswoude J, Ashwell G, Kempf C, Schechter AN, Dean A et al. Receptor-mediated endocytosis of transferrin in K562 cells. J Biol Chem 1983; 258: 4715-4724.
6. Dickinson TK, Connor JR. Histological analysis of selected brain regions of hypotransferrinemic mice. Brain Res 1994; 635: 169-178.
7. Oates PS, Thomas C, Morgan EH. Transferrin receptor activity and localisation in the rat duodenum. Pflugers Archiv: European journal of physiology 2000; 440: 116-124.
8. Knutson M, Menzies S, Connor J, Wessling-Resnick M. Developmental, regional, and cellular expression of SFT/UbcH5A and DMT1 mRNA in brain. J Neurosci Res 2004; 76: 633-641.
9. Farcich EA, Morgan EH. Uptake of transferrin-bound and nontransferrin-bound iron by reticulocytes from the Belgrade laboratory rat: comparison with Wistar rat transferrin and reticulocytes. Am J Hematol 1992; 39: 9-14.
10. Burdo JR, Martin J, Menzies SL, Dolan KG, Romano MA, Fletcher RJ et al. Cellular distribution of iron in the brain of the Belgrade rat. Neuroscience 1999; 93: 1189-1196.
11. Burdo JR, Simpson IA, Menzies S, Beard J, Connor JR. Regulation of the profile of iron-management proteins in brain microvasculature. J Cereb Blood Flow Metab 2004; 24: 67-74.
12. Maher F, Vannucci SJ, Simpson IA. Glucose transporter isoforms in brain: absence of GLUT3 from the blood-brain barrier. J Cereb Blood Flow Metab 1993; 13: 342-345.
13. Simpson IA, Appel NM, Hokari M, Oki J, Holman GD, Maher F et al. Blood-brain barrier glucose transporter: effects of hypo- and hyperglycemia revisited. J Neurochem 1999; 72: 238-247.
14. McCarthy KD, de Vellis J. Preparation of separate astroglial and oligodendroglial cell cultures from rat cerebral tissue. J Cell Biol 1980; 85: 890-902.
15. Antonetti DA, Wolpert EB, De Maio L, Harhaj NS, Scaduto RC, Jr. Hydrocortisone decreases retinal endothelial cell water and solute flux coincident with increased content and decreased phosphorylation of occludin. J Neurochem 2002; 80: 667-677.
16. Yang WM, Jung KJ, Lee MO, Lee YS, Lee YH, Nakagawa S et al. Transient expression of iron transport proteins in the capillary of the developing rat brain. Cell Mol Neurobiol 2011; 31: 93-99.
17. Wu LJ, Leenders AG, Cooperman S, Meyron-Holtz E, Smith S, Land W et al. Expression of the iron transporter ferroportin in synaptic vesicles and the bloodbrain barrier. Brain Res 2004; 1001: 108-117.
18. Bradbury MW. Transport of iron in the blood-brain-cerebrospinal fluid system. J Neurochem 1997; 69: 443-454.
19. Moos T, Morgan EH. Kinetics and distribution of [59Fe-125I]transferrin injected into the ventricular system of the rat. Brain Res 1998; 790: 115-128.
20. Ueda F, Raja KB, Simpson RJ, Trowbridge IS, Bradbury MW. Rate of 59Fe uptake into brain and cerebrospinal fluid and the influence thereon of antibodies against the transferrin receptor. J Neurochem 1993; 60: 106-113.
21. Moos T, Morgan EH. The metabolism of neuronal iron and its pathogenic role in neurological disease: review. Ann NY Acad Sci 2004; 1012: 14-26.
22. Moos T, Morgan EH. The significance of the mutated divalent metal transporter (DMT1) on iron transport into the Belgrade rat brain. J Neurochem 2004; 88: 233-245.
23. Davis RJ, Faucher M, Racaniello LK, Carruthers A, Czech MP. Insulin-like growth factor I and epidermal growth factor regulate the expression of transferrin receptors at the cell surface by distinct mechanisms. J Biol Chem 1987; 262: 13126-13134.
24. Roskams AJ, Connor JR. Aluminum access to the brain: a role for transferrin and its receptor. Proc Natl Acad Sci USA 1990; 87: 9024-9027.
25. Morgan EH, Oates PS. Mechanisms and regulation of intestinal iron absorption. Blood Cells Mol Dis 2002; 29: 384-399.
26. Burdo JR, Menzies SL, Simpson IA, Garrick LM, Garrick MD, Dolan KG et al. Distribution of divalent metal transporter 1 and metal transport protein 1 in the normal and Belgrade rat. J Neurosci Res 2001; 66: 1198-1207.
27. Moos T, Skjoerringe T, Gosk S, Morgan EH. Brain capillary endothelial cells mediate iron transport into the brain by segregating iron from transferrin without the involvement of divalent metal transporter 1. J Neurochem 2006; 98: 1946-1958.
28. Moos T, Rosengren Nielsen T, Skjorringe T, Morgan EH. Iron trafficking inside the brain. J Neurochem 2007; 103: 1730-1740.
29. Farcich EA, Morgan EH. Diminished iron acquisition by cells and tissues of Belgrade laboratory rats. Am J Physiol 1992; 262: R220-R224.
30. Hadziahmetovic M, Song Y, Ponnuru P, Iacovelli J, Hunter A, Haddad N et al. Agedependent retinal iron accumulation and degeneration in hepcidin knockout mice. Invest Ophthalmol Vis Sci 2011; 52: 109-118.
31. Connor JR, Ponnuru P, Wang XS, Patton SM, Allen RP, Earley CJ. Profile of altered brain iron acquisition in restless legs syndrome. Brain 2011; 134: 959-968.
32. Oates PS, Thomas C. Augmented internalisation of ferroportin to late endosomes impairs iron uptake by enterocyte-like IEC-6 cells. Pflugers Archiv: European journal of physiology 2005; 450: 317-325.
33. Hudson DM, Krisinger MJ, Griffiths TA, Macgillivray RT. Neither human hephaestin nor ceruloplasmin forms a stable complex with transferrin. J Cell Biochem 2008; 103: 1849-1855.
34. Burdo JR, Antonetti DA, Wolpert EB, Connor JR. Mechanisms and regulation of transferrin and iron transport in a model blood-brain barrier system. Neuroscience 2003; 121: 883-890.
35. Chen H, Attieh ZK, Dang T, Huang G, van der Hee RM, Vulpe C. Decreased hephaestin expression and activity leads to decreased iron efflux from differentiated Caco2 cells. J Cell Biochem 2009; 107: 803-808.
36. Unger EL, Earley CJ, Thomsen LL, Jones BC, Allen RP. Effects of IV iron isomaltoside-1000 treatment on regional brain iron status in an iron-deficient animal. Neuroscience 2013; 246: 179-185.
37. Chirasani SR, Markovic DS, Synowitz M, Eichler SA, Wisniewski P, Kaminska B et al. Transferrin-receptor-mediated iron accumulation controls proliferation and glutamate release in glioma cells. J Mol Med (Berl) 2009; 87: 153-167.
38. McCarthy RC, Kosman DJ. Ferroportin and exocytoplasmic ferroxidase activity are required for brain microvascular endothelial cell iron efflux. J Biol Chem 2013; 288: 17932-17940.
39. Zhang DL, Senecal T, Ghosh MC, Ollivierre-Wilson H, Tu T, Rouault TA. Hepcidin regulates ferroportin expression and intracellular iron homeostasis of erythroblasts. Blood 2011; 118: 2868-2877.
40. De Domenico I, Nemeth E, Nelson JM, Phillips JD, Ajioka RS, Kay MS et al. The hepcidin-binding site on ferroportin is evolutionarily conserved. Cell Metab 2008; 8: 146-156.