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 production of thiobarbituric acid reactive substances, a marker of lipid peroxidation, and 4-hydroxynonenal (4-HNE), a lipid peroxidation aldehydic product. Incubations with 4-HNE, used at a range of concentrations comparable to those obtained during peroxidation, induced a simultaneous, dose-dependent decrease of dopamine (DA) uptake and Na+/K+ ATPase activity and a loss of sulfhydryl (SH) groups. Similar results were observed in a previous study when lipid peroxidation was induced after incubation of synaptosomes in ascorbic acid. Taken together, these data suggest that 4-HNE is an important mediator 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 contribute to the onset and progression of Parkinson's disease.
Morel
P
P
Center for Study and Research on Xenobiotics, University of Medicine and Pharmacy, Poitiers, France. patricia.morel@wanadoo.fr
Tallineau
C
C
Pontcharraud
R
R
Piriou
A
A
Huguet
F
F
D000447:Aldehydes / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology; D001692:Biological Transport; D003342:Corpus Striatum / Q000187:drug effects* / Q000201:enzymology; D004298:Dopamine / Q000378:metabolism*; D015227:Lipid Peroxidation; D051381:Rats; D017208:Rats, Wistar; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D013438:Sulfhydryl Compounds / Q000378:metabolism; D013574:Synaptosomes / Q000187:drug effects / Q000201:enzymology; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D000447:Aldehydes; D013438:Sulfhydryl Compounds; D017392:Thiobarbituric Acid Reactive Substances; D000254:Sodium-Potassium-Exchanging ATPase; C027576:4-hydroxy-2-nonenal; D001205:Ascorbic Acid; D004298:Dopamine