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

• Published in: The American journal of pathology Vol. 148; no. 1; pp. 89 - 93
• Main Authors: Montine, TJ, Amarnath, V, Martin, ME, Strittmatter, WJ, Graham, DG
• Format: Journal Article
• Language: English
• Published: Bethesda, MD ASIP 01.01.1996; American Society for Investigative Pathology
• Subjects: 3,4-Methylenedioxyamphetamine - chemistry; 3,4-Methylenedioxyamphetamine - pharmacology; Aldehydes - chemistry; Aldehydes - pharmacology; Biological and medical sciences; Carcinoma, Embryonal; Cytoskeletal Proteins - drug effects; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Lipid Peroxidation; Medical sciences; Neuroglia - chemistry; Neuroglia - drug effects; Neurology; tau Proteins - chemistry; Tumor Cells, Cultured; Human; Cell culture; Nervous system diseases; Alzheimer disease; Pathogenesis; Cytotoxicity; Lipids; Crosslinking; Neurofibrillary tangle; In vitro; Cerebral disorder; Proteins; Central nervous system disease; Cytoskeleton; Degenerative disease; Peroxidation
• ISSN: 0002-9440; 1525-2191

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.