title: Comparative effects of Abeta(1-42)-Al complex from rat and human amyloid on rat endothelial cell cultures.
abstract: Metal ions are widely recognized as a key factor for the conformational changes and aggregation of the Alzheimer's disease amyloid (Abeta). So far Al(3+) has received much less attention than other biometals in terms of interaction with Abeta. Brain endothelial cells have been identified as important regulators of the neuronal microenvironment, including Abeta levels. The purpose of this study is to compare the effects of the complex amyloid (Abeta(1-42))-Al, from human and rat, with the effects produced by metal-free Abeta on rat neuroendothelial cells (NECs). To establish Abeta and Abeta-Al toxicity on NECs, survival, vitality, and angiogenesis are evaluated. Cell survival is reduced by human and rat Abeta in a time-dependent manner. This toxic effect is remarkably pronounced in the presence of human Abeta-Al. Moreover, rat Abeta has anti-angiogenic properties on NECs, and this effect is aggravated dramatically by using both human and rat Abeta-Al complexes. The data and arguments presented herein clearly demonstrate the involvement of Al(3+) in Abeta aggregation and, consequently, increasing endothelial cell toxicity.
authors.affiliation: CNR-Institute for Biomedical Technologies, Padova Unit Metalloproteins, Italy.
authors.forename: Denise
authors.initials: D
authors.lastname: Drago
authors.forename: Marcella
authors.initials: M
authors.lastname: Folin
authors.forename: Silvia
authors.initials: S
authors.lastname: Baiguera
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Tognon
authors.forename: Fernanda
authors.initials: F
authors.lastname: Ricchelli
authors.forename: Paolo
authors.initials: P
authors.lastname: Zatta
mesh_terms: D000535:Aluminum / Q000633:toxicity*; D000682:Amyloid / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D001921:Brain / Q000098:blood supply*; D002470:Cell Survival / Q000187:drug effects*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects*; D006801:Humans; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D008854:Microscopy, Electron; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D016874:Neurofibrillary Tangles / Q000187:drug effects / Q000473:pathology; D010084:Oxidation-Reduction; D010446:Peptide Fragments / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000682:Amyloid; D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D000535:Aluminum