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American Journal of Pathology, Vol 148, 89-93, Copyright © 1996 by American Society for Investigative Pathology

REGULAR ARTICLES

E-4-hydroxy-2-nonenal is cytotoxic and cross-links cytoskeletal proteins in P19 neuroglial cultures

TJ Montine, V Amarnath, ME Martin, WJ Strittmatter and DG Graham
Department of Pathology, Duke University Medical Center, Durham, North Carolina, USA.

Lipid peroxidation increases with age in brain and is elevated further in Alzheimer's disease. E-4-hydroxy-2-nonenal and malondialdehyde are products of lipid peroxidation that can adduct and cross-link protein. Neurofibrillary tangles, a feature of Alzheimer's disease composed mostly of tau protein, contain cross-linked and ubiquitin-conjugated protein. In P19 neuroglial cultures, E-4-hydroxy-2-nonenal was a potent cytotoxin that cross-linked cytoskeletal proteins, including tau into high molecular weight species that were conjugated with ubiquitin. Malondialdehyde formed monoadducts with cell protein but did not cross- link and was not cytotoxic. A non-crosslinking analogue of E-4-hydroxy- 2-nonenal was not cytotoxic. E-4-Hydroxy-2-nonenal may contribute to neurodegeneration and neurofibrillary tangle formation in Alzheimer's disease.

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