The mechanism of action of 4-hydroxynonenal in cell injury.
The effect of the C9 ketoaldehyde, 4-hydroxynonenal (HNE), a cytotoxic product of lipid peroxidation, on DNA, RNA and protein synthesis has been investigated in cells in culture. Macromolecular synthesis is powerfully inhibited by this agent which readily enters the lipid-rich membranes and is considerably more toxic than the polar ketoaldehyde, methyl glyoxal (MG). The entry of HNE into membranes lowers their glutathione GSH content. This is associated with an increased lipid peroxidation measured in vitro which is blocked by added GSH or alpha-tocopherol. It is proposed that this latter sequence of events is the underlying cause of the cytopathic effect of HNE in cells in culture.
D000447:Aldehydes / Q000633:toxicity*; D000818:Animals; D002478:Cells, Cultured; D003545:Cysteine / Q000494:pharmacology; D004261:DNA Replication / Q000187:drug effects*; D005978:Glutathione / Q000378:metabolism; D006168:Guinea Pigs; D007700:Kinetics; D008099:Liver / Q000378:metabolism; D008862:Microsomes, Liver / Q000378:metabolism; D014176:Protein Biosynthesis / Q000187:drug effects*; D051381:Rats; D012867:Skin / Q000187:drug effects* / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects*
D000447:Aldehydes; D005978:Glutathione; C027576:4-hydroxy-2-nonenal; D003545:Cysteine