Metal ions such as Fe++ and Cu ++ are reactive cations which are known to catalyze eventivai production of either hydroxyl radical(OH) or singlet oxygen"02´, in the Haber-I-´eiss, reaction. These metal ions hai-e been suggested to stimulate the autoxidation of several autosidizable compounds, among them catecholamines and hemoglobin. The autoxidation of 6-OHDA is also stimulated by metal ions and it is reported that neuronal damages caused by 6-OHDA are affected by metal ions. In the iron-catalyzed Haber-Weiss´ reaction to produce OH- the only function of 0- is to reduce Fe--` to Fe´-. This rove o< 0 mat,: be replaced by other reducing agents and ascorbate may be one of such reducing agents occurinz is biological system. In the present study, the possible role of Fe-- was investigated in the autoxidation of 6-OHD´A and 6-OHDA induced inactivation of synaptosomai Na--K- ATPase and 11g+r ATPase. These effects were studied with respect to generation of reactive oxygen species during autoxidation of 6-OHDA, lipid peroxidation and oxidation of sulfhydryl group. Also, tlhe effect of ascorbate on Inactivation of synaptosomal ATPase caused by 6-OHDA with and without Fe-- was investigated. Tl e synaptoso _ al to--KATPase and M.-ATPase activities were significantly reduced by 6-OHDA, and this inactivation was effectively prevented by catalase, a scavenger of H202, SOD, a scaven;er of 0- and 1_istidine, a scaven er of 102. Generation of HaOa and 0a during autoxidation of 6-OHDA and autoxidation were inhibited by catalase and SOD. Fe` -stimulated the rate of autoxidation of 6-OHDA and enhanced inactivation of ATPase caused by 6-OHDA. Inactivation of ATPase caused by F anal u-OHD A was apparently inhibited by catalase, SOD and histidine. Fe´+ reacted with 02 which was released during autoxidation of 6-OHDA and formed other reactive oxygen species including H20,. iVhen synaptosomes were incubate` with 6-OHDA, both the production of malonyldialdehvde from synaptosomes and t: e oxidation of sulfhydryl groups were increased with time, and these phenomena were further enhanced by Fey+ or Cu´+. Generation of H202 and inactivation of ATPases due to interaction of Fe and 6-OHDA were facilitated b;r as o b te.
The results obtained suggest that reactive oxygen species which tape part in au:oxidation or 6-OHDA or
v=
which ,;-ere released primarily during autoxidation of 6-OHDA may be the less reactive oxygen species
such as Os and immediate oxidants of destructive processes appear to be due to more reacti (-, oxygen species such as =02. Fe++ acted as catalyst for autoxidation of 6-OHD:A and enhanced the inac-Livat;o7L of ATPases caused by 6-OHDA. These- effects were further stimulated by ascorbate. It is therefore sumzested that inactivation of ATPases caused by v-OHD A or Fe,-+ and 6-OHDA may be associated with lipid
peroxicaation and oxidation of sulfhydryl groups of synaptosomes, and these events may be attributable to 02, H202 and particularly, ´-OZ
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