TY - JOUR
T1 - β-amyloid peptide free radical fragments initiate synaptosomal lipoperoxidation in a sequence-specific fashion
T2 - Implications to alzheimer′s disease
AU - Butterfield, D. Allan
AU - Hensley, Kenneth
AU - Harris, Marni
AU - Mattson, Mark
AU - Carney, John
N1 - Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 1994/4/29
Y1 - 1994/4/29
N2 - We have previously reported (Hensley et al., Proc Natl. Acad. Sci USA (1994) in press) that β-amyloid peptide fragments in aqueous media, in a metal-independent reaction, produce reactive peptide free radicals and reactive oxygen species. In contrast to the hours or days necessary to produce neurotoxicity and a detectable free radical for β-amyloid, the extremely neurotoxic Aβ(25-35) fragment of β-amyloid peptide produces a detectable radical in minutes. We now report that Aβ(25-35) is a potent lipoperoxidation initiator, as inferred from peptide-mediated reduction of nitroxyl stearate spin labels bound to rodent neocortical synaptosomal membranes. Aβ(25-35) rapidly quenches the paramagnetism of membrane-bound 12-nitroxyl stearate spin probe deep within the lipid bilayer, but reacts poorly with the 5-nitroxyl isomer whose paramagnetic center is near the lipid/water interface. Aβ(35-25), the non-neurotoxic reverse sequence of Aβ(25-35), shows little proclivity to reduce either spin label. These findings are formulated into a“molecular shrapnel” model of neuronal membrane damage in Alzheimer′s disease.
AB - We have previously reported (Hensley et al., Proc Natl. Acad. Sci USA (1994) in press) that β-amyloid peptide fragments in aqueous media, in a metal-independent reaction, produce reactive peptide free radicals and reactive oxygen species. In contrast to the hours or days necessary to produce neurotoxicity and a detectable free radical for β-amyloid, the extremely neurotoxic Aβ(25-35) fragment of β-amyloid peptide produces a detectable radical in minutes. We now report that Aβ(25-35) is a potent lipoperoxidation initiator, as inferred from peptide-mediated reduction of nitroxyl stearate spin labels bound to rodent neocortical synaptosomal membranes. Aβ(25-35) rapidly quenches the paramagnetism of membrane-bound 12-nitroxyl stearate spin probe deep within the lipid bilayer, but reacts poorly with the 5-nitroxyl isomer whose paramagnetic center is near the lipid/water interface. Aβ(35-25), the non-neurotoxic reverse sequence of Aβ(25-35), shows little proclivity to reduce either spin label. These findings are formulated into a“molecular shrapnel” model of neuronal membrane damage in Alzheimer′s disease.
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U2 - 10.1006/bbrc.1994.1508
DO - 10.1006/bbrc.1994.1508
M3 - Article
C2 - 8179604
AN - SCOPUS:0028178837
SN - 0006-291X
VL - 200
SP - 710
EP - 715
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 2
ER -