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Neurobiology of aging1991; 12(5); 413-418; doi: 10.1016/0197-4580(91)90066-s

Ferritin: the role of aluminum in ferritin function.

Abstract: We previously showed that human brain ferritin (HBF) binds aluminum (Al) in vivo and in vitro and HBF isolated from Alzheimer's brain had more Al bound compared to aged matched controls (7). To further understand the role ferritin may play in Al neurotoxicity, we have studied in vitro the effect of Al on the function of human ferritin isolated from Alzheimer's (AD) and normal brain tissue, and compared the results with other mammalian ferritins. Al causes a concentration-dependent decrease in the initial rate of iron loading into apo-horse spleen and human brain ferritin and the rates were similar for ferritin isolated from both AD and normal brains. The rates of iron release of mammalian ferritins from different tissues were determined: horse spleen much greater than human liver greater than rat brain greater than human brain = rat liver ferritin. The rates of iron release of AD and normal human brain ferritin were similar and were unaffected by preloading with Al. Several mammalian ferritins were compared for their total iron uptake: horse spleen = human liver greater than human brain (normal) = human brain (AD) ferritin. In 20 mM HEPES (pH 6.0) buffer holoferritin is more resistant to precipitation by Al than apoferritin suggesting that holoferritin is a better chelator for nonferrous metal ions.
Publication Date: 1991-09-01 PubMed ID: 1770974DOI: 10.1016/0197-4580(91)90066-sGoogle Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

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The research article investigates the relationship between aluminum and ferritin, a protein that stores iron, particularly in the context of Alzheimer’s disease. The research found that aluminum affects the rate at which iron is loaded into the ferritin protein, with the possibility of ferritin playing a role in aluminum neurotoxicity in Alzheimer’s disease.

Objective of the Research

  • The primary goal of this research study was to explore the potential role ferritin might play in Aluminum (Al) neurotoxicity which is potentially linked to the development of Alzheimer’s disease.

Aluminum Interference with Iron Loading

  • The researchers discovered that aluminum can cause a concentration-dependent decrease in the initial rate of iron loading into both horse spleen and human brain ferritin.
  • These alterations were observed in ferritin isolated from both Alzheimer’s afflicted and normal brain tissues.
  • It implies that aluminum can interact with the ferritin protein in ways that may affect its standard mechanism of action.

Rate of Iron Release

  • Different types of mammalian ferritins were compared to understand their iron release rates.
  • The rates were found to be highest in horse spleen ferritin, intermediate in human liver ferritin, and lowest in both the human brain and rat liver ferritin.
  • No significant differences were noted between ferritin isolated from Alzheimer’s and normal human brain tissue, and notably, these rates remained unaffected by preloading with aluminum.

Total Iron Uptake

  • When investigating total iron uptake, horse spleen and human liver ferritin showed higher uptake rates than human brain ferritin (from both normal and Alzheimer’s diseased brains).

Reaction to Aluminum

  • Apart from affecting iron loading into ferritin, aluminum was also found to impact the tendency of ferritin to precipitate.
  • Interestingly, in a 20 mM HEPES buffer at pH 6.0, holoferritin (iron-loaded ferritin) proved to resist precipitation by aluminum more than apoferritin (iron-free ferritin), suggesting that holoferritin could be a more efficient chelator for nonferrous metal ions.

Implications of the Study

  • This research could be deeply significant in the study of neurodegenerative disorders like Alzheimer’s disease. The interaction between ferritin and aluminum, and how it might potentially influence the disease’s pathogenesis, could open up new paths for therapeutic interventions.

Cite This Article

APA
Fleming JT, Joshi JG. (1991). Ferritin: the role of aluminum in ferritin function. Neurobiol Aging, 12(5), 413-418. https://doi.org/10.1016/0197-4580(91)90066-s

Publication

ISSN: 0197-4580
NlmUniqueID: 8100437
Country: United States
Language: English
Volume: 12
Issue: 5
Pages: 413-418

Researcher Affiliations

Fleming, J T
  • Department of Biochemistry, University of Tennessee, Knoxville 37996-0840.
Joshi, J G

    MeSH Terms

    • Aluminum / pharmacology
    • Animals
    • Brain Chemistry / drug effects
    • Electrophoresis, Polyacrylamide Gel
    • Ferritins / chemistry
    • Ferritins / isolation & purification
    • Ferritins / metabolism
    • Horses
    • Humans
    • Iron / metabolism
    • Iron / pharmacology
    • Liver / metabolism
    • Protein Binding / drug effects
    • Rats
    • Spleen / metabolism

    Citations

    This article has been cited 5 times.
    1. Bartzokis G, Lu PH, Tishler TA, Peters DG, Kosenko A, Barrall KA, Finn JP, Villablanca P, Laub G, Altshuler LL, Geschwind DH, Mintz J, Neely E, Connor JR. Prevalent iron metabolism gene variants associated with increased brain ferritin iron in healthy older men. J Alzheimers Dis 2010;20(1):333-41.
      doi: 10.3233/JAD-2010-1368pubmed: 20164577google scholar: lookup
    2. DeVoto E, Yokel RA. The biological speciation and toxicokinetics of aluminum. Environ Health Perspect 1994 Nov;102(11):940-51.
      doi: 10.1289/ehp.94102940pubmed: 9738208google scholar: lookup
    3. Iancu TC, Perl DP, Sternlieb I, Lerner A, Leshinsky E, Kolodny EH, Hsu A, Good PF. The application of laser microprobe mass analysis to the study of biological material. Biometals 1996 Jan;9(1):57-65.
      doi: 10.1007/BF00188091pubmed: 8574093google scholar: lookup
    4. Joshi JG, Dhar M, Clauberg M, Chauthaiwale V. Iron and aluminum homeostasis in neural disorders. Environ Health Perspect 1994 Sep;102 Suppl 3(Suppl 3):207-13.
      doi: 10.1289/ehp.94102s3207pubmed: 7843099google scholar: lookup
    5. Clauberg M, Joshi JG. Regulation of serine protease activity by aluminum: implications for Alzheimer disease. Proc Natl Acad Sci U S A 1993 Feb 1;90(3):1009-12.
      doi: 10.1073/pnas.90.3.1009pubmed: 7679214google scholar: lookup