E-4-hydroxy-2-nonenal is cytotoxic and cross-links cytoskeletal proteins in P19 neuroglial cultures.
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.
Montine
T J
TJ
Department of Pathology, Duke University Medical Center, Durham, North Carolina, USA.
Amarnath
V
V
Martin
M E
ME
Strittmatter
W J
WJ
Graham
D G
DG
D015104:3,4-Methylenedioxyamphetamine / Q000737:chemistry / Q000494:pharmacology*; D000447:Aldehydes / Q000737:chemistry / Q000494:pharmacology*; D018236:Carcinoma, Embryonal; D003598:Cytoskeletal Proteins / Q000187:drug effects*; D015227:Lipid Peroxidation; D009457:Neuroglia / Q000737:chemistry / Q000187:drug effects*; D014407:Tumor Cells, Cultured; D016875:tau Proteins / Q000737:chemistry
D000447:Aldehydes; D003598:Cytoskeletal Proteins; D016875:tau Proteins; D015104:3,4-Methylenedioxyamphetamine; C027576:4-hydroxy-2-nonenal