beta-Amyloid-induced toxicity in rat hippocampal cells: in vitro evidence for the involvement of free radicals.
The conditions under which amyloid is toxic to primary rat hippocampal neurons were investigated. Synthetic A beta (1-42) peptide elicited neurotoxic activity following "aging" for 7 to 14 days at 37 degrees C in Modified Eagles Media. Neurotoxicity included decreases in neurite length, cell number, and a loss in 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide reduction. In contrast, the addition of the media supplement B27, during the aging process, promoted the neurotrophic actions of aged A beta (1-42), as indicated by an increase in neurite length and the number of cells possessing neurites, and attenuated toxicity. The differences in the biological actions elicited by these two preparations of aged peptide were attributed to the presence of the B27 components. B27 consists of a mixture of agents that provide protection against oxidative damage. In support, aging A beta (1-42) in the presence of superoxide dismutase and catalase, two components of B27, significantly reduced the toxic actions of peptide; hence, suggesting that free radicals may be required for the toxicity that accumulates during the aging of the peptide. To determine the contribution of particular amino acid residues in amyloid toxicity, studies were carried out with an aged preparation of the A beta (1-42) analog, A beta (1-42)Nle35. Findings from these studies suggest that the methionine residue may play a part, but is not required, for amyloid toxicity to occur.
Manelli
A M
AM
Department 47U, Abbott Laboratories, Abbott Park, IL 60064-3500, USA.
Puttfarcken
P S
PS
D000544:Alzheimer Disease / Q000378:metabolism*; D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D002452:Cell Count / Q000187:drug effects; D005609:Free Radicals; D006624:Hippocampus / Q000187:drug effects*; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D051381:Rats; D017207:Rats, Sprague-Dawley
D016229:Amyloid beta-Peptides; D005609:Free Radicals