E-4-hydroxy-2-nonenal is Cytotoxic and Cross-links Cytoskeletal Proteins in P19 Neuroglial Cultures

Overview

Journal Am J Pathol

Publisher Elsevier

Specialty Pathology

Date 1996 Jan 1

PMID 8546230

Citations 27

Authors

T J Montine

V Amarnath

M E Martin

W J Strittmatter

D G Graham

Affiliations

Soon will be listed here.

Abstract

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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