Origin of 4-hydroxynonenal incubation-induced inhibition of dopamine transporter and Na+/K+ adenosine triphosphate in rat striatal synaptosomes

Abstract Previous experiments reported that an incubation of striatal synaptosomes with 4-hydroxynonenal (4-HNE) resulted in an inhibition of dopamine (DA) uptake and Na + /K + adenosine triphosphate (ATPase) activity. The present work investigated whether theses inhibitions are related to a 4-HNE binding to the DA transporter (DAT) and the Na + /K + ATPase. The number of specific [ 125 I]-PE2I binding sites on the DAT was significantly reduced after incubation with 4-HNE. The Na + /K + ATPase activity decrease induced by 4-HNE was partially reversed, in a dose-dependent manner, by veratridine, a pump stimulator agent. Our previous data (Morel, P., Tallineau, C., Pontcharraud, R., Piriou, A. and Huguet, F., Effects of 4-hydroxynonenal, a lipid peroxidation product, on dopamine transport and Na + /K + ATPase in rat striatal synaptosomes. Neurochem. Int., 33 (1999) 531–540) combining with the data observed in this study suggest that changes in DA uptake in striatal synaptosomes are directly related to 4-HNE binding to the DAT, whereas the decrease in Na + /K + ATPase activity resulted only partially from 4-HNE binding to the pump and is mainly secondary to membrane lipid disruption.