Copper transfer from Cu-Aβ to human serum albumin inhibits aggregation, radical production and reduces Aβ toxicity

Lorena Perrone, Emmanuelle Mothes, Maeva Vignes, Anaïs Mockel, Cindy Figueroa, Marie Christine Miquel, Marie Lise Maddelein, Peter Faller*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

Amyloid-β peptides (Aβ) and the protein human serum albumin (HSA) interact in vivo. They are both localised in the blood plasma and in the cerebrospinal fluid. Among other functions, HSA is involved in the transport of the essential metal copper. Complexes between Aβ and copper ions have been proposed to be an aberrant interaction implicated in the development of Alzheimer's disease, where Cu is involved in Aβ aggregation and production of reactive oxygen species (ROS). In the present work, we studied copper-exchange reaction between Aβ and HSA or the tetrapeptide DAHK (N-terminal Cu-binding domain of HSA) and the consequence of this exchange on Aβ-induced ROS production and cell toxicity. The following results were obtained: 1) HSA and DAHK removed CuII from Ab rapidly and stoichiometrically, 2) HSA and DAHK were able to decrease Cu-induced aggregation of Aβ, 3) HSA and DAHK suppressed the catalytic HO· production in vitro and ROS production in neuroblastoma cells generated by Cu-Aβ and ascorbate, 4) HSA and DAHK were able to rescue these cells from the toxicity of Cu-Aβ with ascorbate, 5) DAHK was more potent in ROS suppression and restoration of neuroblastoma cell viability than HSA, in correlation with an easier reduction of CuII-HSA than Cu-DAHK by ascorbate, in vitro. Our data suggest that HSA is able to decrease aberrant CuII-Aβ interaction. The repercussion of the competition between HSA and Ab to bind Cu in the blood and brain and its relation to Alzheimer's disease are discussed.

Original languageEnglish
JournalChemBioChem
Volume11
Issue number1
Pages (from-to)110-118
Number of pages9
ISSN1439-4227
DOIs
Publication statusPublished - 4. Jan 2010

Keywords

  • Amyloid beta-peptides
  • Bioinorganic chemistry
  • Copper
  • Human serum albumin
  • Reactive oxygen species

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