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

Del Giudice, Rita LU ; Pesce, Alessandra ; Cozzolino, Flora ; Monti, Maria ; Relini, Annalisa ; Piccoli, Renata ; Arciello, Angela and Monti, Daria Maria (2018) In BioMetals 31(4). p.551-559
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... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Amyloidosis, ApoA-I, Conformational analysis, Iron, Protein aggregation
in
BioMetals
volume
31
issue
4
pages
551 - 559
publisher
Springer
external identifiers
  • pmid:29623474
  • scopus:85045070079
ISSN
0966-0844
DOI
10.1007/s10534-018-0101-y
language
English
LU publication?
yes
id
cb60405e-45d5-4b5f-a5d4-616365e83791
date added to LUP
2018-04-18 14:59:31
date last changed
2021-09-29 03:14:27
@article{cb60405e-45d5-4b5f-a5d4-616365e83791,
  abstract     = {<p>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.</p>},
  author       = {Del Giudice, Rita and Pesce, Alessandra and Cozzolino, Flora and Monti, Maria and Relini, Annalisa and Piccoli, Renata and Arciello, Angela and Monti, Daria Maria},
  issn         = {0966-0844},
  language     = {eng},
  number       = {4},
  pages        = {551--559},
  publisher    = {Springer},
  series       = {BioMetals},
  title        = {Effects of iron on the aggregation propensity of the N-terminal fibrillogenic polypeptide of human apolipoprotein A-I},
  url          = {http://dx.doi.org/10.1007/s10534-018-0101-y},
  doi          = {10.1007/s10534-018-0101-y},
  volume       = {31},
  year         = {2018},
}