Neurofilaments are the major neuronal target of hydroxynonenal-mediated protein cross-links

Abstract Lipid peroxidation generates reactive aldehydes, most notably hydroxynonenal (HNE), which covalently binds amino acid residue side chains leading to protein inactivation and insolubility. Specific adducts of lipid peroxidation have been demonstrated to be intimately associated with patholog...

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Bibliographic Details
Published in:Free radical research 2013-07, Vol.47 (6-7), p.507-510
Main Authors: Perry, E. A., Castellani, R. J., Moreira, P. I., Nunomura, A., Lui, Q., Harris, P. L. R., Sayre, L. M., Szweda, P. A., Szweda, L. I., Zhu, X., Smith, M. A., Perry, G.
Format: Article
Language:English
Subjects:
Aldehydes - chemistry
Alzheimer disease
Animals
Antibodies - immunology
axon
cytoskeleton
Fluorescence
lipid peroxidation
Lysine - chemistry
Lysine - immunology
Mice
Mice, Inbred Strains
neurofibrillary tangle
Neurofilament Proteins - chemistry
Neurofilament Proteins - metabolism
oxidative stress
Sciatic Nerve - chemistry
Sciatic Nerve - cytology
Sciatic Nerve - metabolism
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Summary:Abstract Lipid peroxidation generates reactive aldehydes, most notably hydroxynonenal (HNE), which covalently binds amino acid residue side chains leading to protein inactivation and insolubility. Specific adducts of lipid peroxidation have been demonstrated to be intimately associated with pathological lesions of Alzheimer's disease (AD), suggesting that oxidative stress is a major component in the disease. Here, we examined the HNE-cross-linking modifications by using an antibody specific for a lysine-lysine cross-link. Since in a prior study we noted no immunolabeling of neuritic plaques or neurofibrillary tangles but instead found strong labeling of axons, we focused this study on axons. Axonal labeling was examined in mouse sciatic nerve, and immunoblotting showed the cross-link was restricted to neurofilament heavy and medium subunits, which while altering migration, did not indicate larger NF aggregates, indicative of intermolecular cross-links. Examination of mice at various ages showed the extent of modification remaining relatively constant through the life span. These findings demonstrate lipid-cross-linking peroxidation primarily involves lysine-rich neurofilaments and is restricted to intramolecular cross-links.
ISSN:1071-5762
1029-2470
DOI:10.3109/10715762.2013.794265