Iron and free radical oxidations in cell membranes.
Iron and free radical oxidations in cell membranes.
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发表时间：
2000-05
影响因子：
1.6
通讯作者：
Freya Q. Schafer;Steven Y. Qian;Garry R. Buettner
中科院分区：
文献类型：
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作者：
Freya Q. Schafer;Steven Y. Qian;Garry R. Buettner
脑组织富含多不饱和脂肪酸，对脂质过氧化反应非常敏感。铁是一种重要的自由基氧化引发剂。我们建议，铁介导的脂质过氧化的主要途径是通过铁-氧复合物，而不是铁与过氧化氢的反应，芬顿反应。为了验证这一假设，我们用二十二碳六烯酸（DHA）富集白血病细胞（K-562和L1210细胞）作为脑组织的模型，将DHA的量从约3摩尔%增加到32摩尔%。这些细胞，然后进行亚铁和分子氧启动脂质过氧化作用的存在或不存在的过氧化氢。使用EPR自旋捕获与α-（4-吡啶基-1-氧化物）-N-叔丁基硝酮（POBN）检测脂质衍生的自由基。正如预期的那样，脂质衍生的自由基形成随着细胞脂质不饱和度的增加而增加。去铁醛的实验表明，铁是这些细胞形成脂质自由基所必需的。此外，铁DHA富集L1210细胞导致大量的自由基形成，自由基形成增加铁的量增加。然而，在加入亚铁之前，细胞暴露于过氧化氢并没有增加细胞自由基的形成，但实际上减少了自旋加合物的形成。这些数据表明，铁-氧复合物是引发生物自由基氧化的主要途径。该模型提出了一种机制来解释脑组织中的催化铁如何具有如此大的破坏性。
Brain tissue being rich in polyunsaturated fatty acids, is very susceptible to lipid peroxidation. Iron is well known to be an important initiator of free radical oxidations. We propose that the principal route to iron-mediated lipid peroxidations is via iron-oxygen complexes rather than the reaction of iron with hydrogen peroxide, the Fenton reaction. To test this hypothesis, we enriched leukemia cells (K-562 and L1210 cells) with docosahexaenoic acid (DHA) as a model for brain tissue, increasing the amount of DHA from approximately 3 mole % to 32 mole %. These cells were then subjected to ferrous iron and dioxygen to initiate lipid peroxidation in the presence or absence of hydrogen peroxide. Lipid-derived radicals were detected using EPR spin trapping with alpha-(4-pyridyl-1-oxide)-N-t-butylnitrone (POBN). As expected, lipid-derived radical formation increases with increasing cellular lipid unsaturation. Experiments with desferal demonstrate that iron is required for the formation of lipid radicals from these cells. Addition of iron to DHA-enriched L1210 cells resulted in significant amounts of radical formation; radical formation increased with increasing amount of iron. However, the exposure of cells to hydrogen peroxide before the addition of ferrous iron did not increase cellular radical formation, but actually decreased spin adduct formation. These data suggest that iron-oxygen complexes are the primary route to the initiation of biological free radical oxidations. This model proposes a mechanism to explain how catalytic iron in brain tissue can be so destructive.