Protein-bound acrolein: A novel marker of oxidative stress in Alzheimer's disease

被引:332
作者
Calingasan, NY
Uchida, K
Gibson, GE
机构
[1] Cornell Univ, Coll Med, Burke Med Res Inst, Dept Neurol & Neurosci, White Plains, NY 10605 USA
[2] Nagoya Univ, Lab Food & Biodynam, Grad Sch Bioagr Sci, Nagoya, Aichi, Japan
关键词
Alzheimer's disease; oxidative stress; acrolein; neurofibrillary tangles; lipid peroxidation; hydroxynonenal;
D O I
10.1046/j.1471-4159.1999.0720751.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Several lines of evidence support the role of oxidative stress, including increased lipid peroxidation, in the pathogenesis of Alzheimer's disease (AD). Lipid peroxidation generates various reactive aldehydes, such as 4-hydroxynonenal (HNE), which have been detected immunochemically in AD, particularly in neurofibrillary tangles, one of the major diagnostic lesions in AD brains. A recent study demonstrated that acrolein, the most reactive among the alpha,beta-unsaturated aldehyde products of lipid peroxidation, could be rapidly incorporated into proteins, generating a carbonyl derivative, a marker of oxidative stress to proteins. The current studies used an antibody raised against acrolein-modified keyhole limpet hemocyanin (KLH) to test whether acrolein modification of proteins occurs in AD. Double immunofluorescence revealed strong acrolein-KLH immunoreactivity in more than half of all paired helical filament (PHF)-1-labeled neurofibrillary tangles in AD cases. Acrolein-KLH immunoreactivity was also evident in a few neurons lacking PHF-1-positive neurofibrillary tangles. Light acrolein-KLH immunoreactivity occurred in dystrophic neurites surrounding the amyloid-beta core, which itself lacked acrolein-KLH staining. The pattern of acrolein-KLH immunostaining was similar to that of HNE. Control brains did not contain any acrolein-KLH-immunoreactive structures. The current results suggest that protein-bound acrolein is a powerful marker of oxidative damage to protein and support the hypothesis that lipid peroxidation and oxidative damage to protein may play a crucial role in the formation of neurofibrillary tangles and to neuronal death in AD.
引用
收藏
页码:751 / 756
页数:6
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