Comparative effects of Abeta(1-42)-Al complex from rat and human amyloid on rat endothelial cell cultures.
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.
Drago
Denise
D
CNR-Institute for Biomedical Technologies, Padova Unit Metalloproteins, Italy.
Folin
Marcella
M
Baiguera
Silvia
S
Tognon
Giuseppe
G
Ricchelli
Fernanda
F
Zatta
Paolo
P
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
D000682:Amyloid; D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D000535:Aluminum