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BioMetals

, Volume 31, Issue 4, pp 551–559 | Cite as

Effects of iron on the aggregation propensity of the N-terminal fibrillogenic polypeptide of human apolipoprotein A-I

  • Rita Del Giudice
  • Alessandra Pesce
  • Flora Cozzolino
  • Maria Monti
  • Annalisa Relini
  • Renata Piccoli
  • Angela Arciello
  • Daria Maria Monti
Article

Abstract

Specific mutations in APOA1 gene lead to systemic, hereditary amyloidoses. In ApoA-I related amyloidosis involving the heart, amyloid deposits are mainly constituted by the 93-residue N-terminal region of the protein, here indicated as [1-93]ApoA-I. Oxidative stress is known to be an enhancing factor for protein aggregation. In healthy conditions, humans are able to counteract the formation and the effects of oxidative molecules. However, aging and atmospheric pollution increase the concentration of oxidative agents, such as metal ions. As the main effect of iron deregulation is proposed to be an increase in oxidative stress, we analysed the effects of iron on [1-93]ApoA-I aggregation. By using different biochemical approaches, we demonstrated that Fe(II) is able to reduce the formation of [1-93]ApoA-I fibrillar species, probably by stabilizing its monomeric form, whereas Fe(III) shows a positive effect on polypeptide fibrillogenesis. We hypothesize that, in healthy conditions, Fe(III) is reduced by the organism to Fe(II), thus inhibiting amyloid formation, whereas during ageing such protective mechanisms decline, thus exposing the organism to higher oxidative stress levels, which are also related to an increase in Fe(III). This alteration could contribute to the pathogenesis of amyloidosis.

Keywords

Protein aggregation Conformational analysis ApoA-I Amyloidosis Iron 

Notes

Acknowledgements

We thank Dr. Amanda Penco for helping in AFM analyses.

Supplementary material

10534_2018_101_MOESM1_ESM.docx (354 kb)
Supplementary material 1 (DOCX 354 kb)

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Rita Del Giudice
    • 1
    • 2
  • Alessandra Pesce
    • 3
  • Flora Cozzolino
    • 1
    • 4
  • Maria Monti
    • 1
    • 5
  • Annalisa Relini
    • 5
    • 6
  • Renata Piccoli
    • 1
    • 5
  • Angela Arciello
    • 1
    • 5
  • Daria Maria Monti
    • 1
    • 5
  1. 1.Department of Chemical SciencesUniversity of Naples Federico IINaplesItaly
  2. 2.Department of Experimental Medical ScienceLund UniversityLundSweden
  3. 3.Department of PhysicsUniversity of GenoaGenoaItaly
  4. 4.CEINGE Biotecnologie Avanzate s.c.a r.l.NaplesItaly
  5. 5.Istituto Nazionale di Biostrutture e Biosistemi (INBB)RomeItaly
  6. 6.Department of Chemistry and Industrial ChemistryUniversity of GenoaGenoaItaly

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