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Complexes between A\u03b2 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\u03b2 aggregation and production of reactive oxygen species (ROS). In the present work, we studied copper\u2010exchange reaction between A\u03b2 and HSA or the tetrapeptide DAHK (N\u2010terminal Cu\u2010binding domain of HSA) and the consequence of this exchange on A\u03b2\u2010induced ROS production and cell toxicity. The following results were obtained: 1) HSA and DAHK removed Cu<jats:sup>II<\/jats:sup> from A\u03b2 rapidly and stoichiometrically, 2) HSA and DAHK were able to decrease Cu\u2010induced aggregation of A\u03b2, 3) HSA and DAHK suppressed the catalytic HO<jats:sup>.<\/jats:sup> production in vitro and ROS production in neuroblastoma cells generated by Cu\u2013A\u03b2 and ascorbate, 4) HSA and DAHK were able to rescue these cells from the toxicity of Cu\u2013A\u03b2 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<jats:sup>II<\/jats:sup>\u2013HSA than Cu\u2013DAHK by ascorbate, in vitro. Our data suggest that HSA is able to decrease aberrant Cu<jats:sup>II<\/jats:sup>\u2013A\u03b2 interaction. The repercussion of the competition between HSA and A\u03b2 to bind Cu in the blood and brain and its relation to Alzheimer's disease are discussed.<\/jats:italic><\/jats:p>","DOI":"10.1002\/cbic.200900474","type":"journal-article","created":{"date-parts":[[2009,11,24]],"date-time":"2009-11-24T01:01:00Z","timestamp":1259024460000},"page":"110-118","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":86,"title":["Copper Transfer from Cu\u2013A\u03b2 to Human Serum Albumin Inhibits Aggregation, Radical Production and Reduces A\u03b2 Toxicity"],"prefix":"10.1002","volume":"11","author":[{"given":"Lorena","family":"Perrone","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuelle","family":"Mothes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maeva","family":"Vignes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana\u00efs","family":"Mockel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cindy","family":"Figueroa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie\u2010Christine","family":"Miquel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie\u2010Lise","family":"Maddelein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Faller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,12,23]]},"reference":[{"key":"e_1_2_6_1_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1074069"},{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1132814"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature02621"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1072994"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.2001.81.2.741"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2004.02.010"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2007.07.013"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-2006-102-303"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamem.2007.02.002"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi990438f"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-510X(98)00092-6"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsb.2005.09.004"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi0272151"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1021\/jp710806s"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1039\/B813398K"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.21.12817"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.52.37111"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1002\/cbic.200600319"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi702423h"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja0488028"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi900254n"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja808073b"},{"key":"e_1_2_6_23_2","doi-asserted-by":"publisher","DOI":"10.1002\/cbic.200700111"},{"key":"e_1_2_6_24_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M206428200"},{"key":"e_1_2_6_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jinorgbio.2004.03.001"},{"key":"e_1_2_6_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2003.11.004"},{"key":"e_1_2_6_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biochi.2009.03.013"},{"key":"e_1_2_6_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0009-8981(01)00573-3"},{"key":"e_1_2_6_29_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi00307a046"},{"key":"e_1_2_6_30_2","doi-asserted-by":"publisher","DOI":"10.1139\/o91-121"},{"key":"e_1_2_6_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0162-0134(98)00010-5"},{"key":"e_1_2_6_32_2","doi-asserted-by":"publisher","DOI":"10.1021\/ic951005d"},{"key":"e_1_2_6_33_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi061783p"},{"key":"e_1_2_6_34_2","doi-asserted-by":"crossref","first-page":"21533","DOI":"10.1016\/S0021-9258(20)80574-2","volume":"268","author":"Masuoka J.","year":"1993","journal-title":"J. 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