6-Hydroxydopamine(6-OHDA) is selectively accumulated in catecholamine-containing neurons and causes
r degeneration of nerve terminals when injected into animals. However, the exact molecular mechanism of toxicity remains uncertain. 6-OHDA is an unstable compound which autoxidiaes extremely rapidly. Among the various metal ions, Cu" is an extremely reactive cation which is known to stimulate the autoxidation of several´autoxidizable compounds, among them catecholes and hemoglobin. In the present study, role of Cu"´ was observed on both the production of reactive oxygen species and the inactivation of rat brain, synaptosomal Na+-$+ ATPase and 1big++ATPase caused by 6-OHDA. Synaptosomal Na+-K+ ATPase and Mg" ATPase activities were significantly reduced by 6-OHDA. In reaction medium of pH 7.4 6-OHDA is,
1 autoxidized rapidly and dur.ng this process H202 and superoxide radical(Oz) were formed. Thus, the obse rved findings suggest that inactivation of these ATPases may be caused by reactive oxygen species. Cu--stimulated the rate of autoxidation of 6-OHDA in a dose dependent manner and this stimulation of the autoxidation of 6-OHDA by Cu++ was prevented by EDTA, penicillamine, catalase and histidine. _Effect of Cu++ was also observed with Na+-K+ ATPase and Mg++ ATPase activities. Inhibition of Na+-K+ ATPase and Mg+-ATPase activities by 6-OHDA was further enhanced by Cu++ and these effects were effectively prevented by catalase and histidine. From the results obtained, it is suggested that Cu++ stimulates the autoxidation of 6-OHDA and enhances the inactivation of synaptosomal Na+-K+ ATPase by 6-OHDA. Also, the inactivation of these ATPase may be attributed to singlet oxygen (01).
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