期刊
CHEMBIOCHEM
卷 11, 期 1, 页码 110-118出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/cbic.200900474
关键词
amyloid beta-peptides; bioinorganic chemistry; copper; human serum albumin; reactive oxygen species
资金
- US/France REU
- CNRS Life Science department
- Foundation for Medical Research (FRM)
- European Community [224892]
Amyloid-beta peptides (A beta) 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 A beta and copper ions have been proposed to be an aberrant interaction implicated in the development of Alzheimer's disease, where Cu is involved in A beta aggregation and production of reactive oxygen species (ROS). In the present work, we studied copper-exchange reaction between A beta and HSA or the tetrapepticle DAHK (N-terminal Cu-binding domain of HSA) and the consequence of this exchange on A beta-induced ROS production and cell toxicity. The following results were obtained: 1) HSA and DAHK removed Cu-II from A beta rapidly and stoichiometrically, 2) HSA and DAHK were able to decrease Cu-induced aggregation of A beta, 3) HSA and DAHK suppressed the catalytic HO center dot production in vitro and ROS production in neuroblastoma cells generated by Cu-A beta and ascorbate, 4) HSA and DAHK were able to rescue these cells from the toxicity of Cu-A beta 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 Cu-II-HSA than Cu-DAHK by ascorbate, in vitro. Our data suggest that HSA is able to decrease aberrant Cu-II-A beta interaction. The repercussion of the competition between HSA and A beta to bind Cu in the blood and brain and its relation to Alzheimer's disease are discussed.
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