Effects of 4-hydroxynonenal, a lipid peroxidation product, on dopamine transport and Na+/K+ ATPase in rat striatal synaptosomes

Incubation of rat striatal synaptosomes in ascorbic acid induced the produc tion of thiobarbituric acid reactive substances, a marker of lipid peroxida tion, and 4-hydroxynonenal (4-HNE), a lipid peroxidation aldehydic product. Incubations with 4-HNE, used at a range of concentrations comparable to th ose obtained during peroxidation, induced a simultaneous, dose-dependent de crease of dopamine (DA) uptake and Na+/K+ ATPase activity and a loss of sul fhydryl (SH) groups. Similar results were observed in a previous study when lipid peroxidation was induced after incubation of synaptosomes in ascorbi c acid. Taken together, these data suggest that 4-HNE is an important media tor of oxidative stress and may alter DA uptake after binding to SH groups of the DA transporter and to Na+/K+ ATPase. These toxic events may contribu te to the onset and progression of Parkinson's disease. (C) 1999 Elsevier S cience Ltd. All rights reserved.