Fe^++이 6-Hydroxydopamine에 의한 Synaptosome의 변성에 미치는 영향 = Effect of Fe^++ on Degeneration of Synaptosome caused by 6-Hydroxydopamine

다국어 초록 (Multilingual Abstract)

Metal ions such as Fe^++ and Cu^++ are reactive cations which are know to catalyze eventual production of either hydroxyl radical(OHㆍ) or singlet oxygen(^10_2) In the Haber-Weiss reaction. These metal ions have been suggested to simulate the autoxidation of several autoxidizable 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 OHㆍ the only function of 0^-_2 is to reduce Fe^+++ to Fe^++. This role or 0^-_2 may be replaced by other reducing agents and ascorbate may be one of such reducing agents occuring in bioiogical system. In the present study, the possible role of Fe^++ was investigated in the autoxidation of 6-OHDA and 6-OHDA induced inactivation of synaptoiomal Na^+-K+ ATPase and Mg^++ 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, the effect of ascorbate on inactivation of synaptosomal ATPase caused by 6-OHDA with and without Fe^++ was investigated. The synaptosomal Na^+- K^+ ATPase and Mg^++ ATPase activities were significantly reduced by S-OHDA, and this inactivation was effectively prevented by catalase, a scavenger of H_2O_2, SOD, a scavenger of 0^-_2 and histidine, a scavenger of ^1O_2. Generation of H_2O_2 and 0_2 during autoxidation of 6-OHDA and antoxidation were inhibited by catalase and SOD. Fe^++ stimulated the rate of autoxidation og 6-OHDA and enhance inactivation of ATPase caused by 6-0HDA. Inactivation of ATPase caused by Fe^++ and 6-0HDA was apparently inhibited by catalase, SOD and histidine. Fe^++ reacted with O^-_2 which was released during autoxidation of 6-OHDA and formed other reactive oxygen species including H_2O_2. When synaptosomes were incubated with 6-OHDA, both the production of malonyldiaidehyde from synaptosomes and the oxidation of sulfhydryl groups were increased with time, and these phenomena were further enhanced by Fe^++ or Cu^++ Generation of H_20_2 and inactivation of ATPases due to interaction of Fe^++ and 6-OHDA were faciliated by ascorbate. The results obtained suggest that reactive oxygen species which take pare in autoxidation of 6-OHDA or which were released primarily during autoxidation of 6-OHDA may be the less reactive oxygen species such as 0^-_2 and Immediate oxidants of destruction processes appear to be due to more reactive oxygen species such as ^1O_2 Fe^++ acted as catalyst for autoxidation of 6-0HDA and enhanced the inactivation of ATPases caused by 6-OHDA. These effects were further stimulated by ascorbate. It is therefore suggested that inactivation of ATPases caused by 6-OHDA or Fe^++ and 6-OHDA may be associated with lipid peroxidation and oxidation of sulfhydryl groups of synaptosomes, and these events may be attributable to O_2, H_2O_2 and particularly, ^1O_2.