Oxidation of 4-hydroxynonenal in rat brain slices.

4-Hydroxy-2-nonenal (HNE) is implicated as a neurotoxic 'second messenger' of oxidative damage in Alzheimer's disease (AD). The mechanism of HNE toxicity is due to alkylation of cellular nucleophilic groups. The C1 aldehyde is key to the alkylation ability of HNE. Oxidation of the C1 aldehyde to 4-hydroxy-2-nonenoic acid is catalyzed by aldehyde dehydrogenases. In this work, we tested the hypothesis that HNE oxidation to HNEAcid occurs in rat cerebral cortex utilizing rat cerebral cortical slices exposed extracellularly to HNE. HNEAcid formation occurs in a dose dependent manner with approximately 18-25% of the HNE consumed accounted for by HNEAcid formation. HNEAcid was found exclusively in the incubation media, suggesting that HNEAcid is exported from the cells of the slice. These data demonstrate that HNE detoxification through the oxidation pathway occur in the cerebral cortex.