Pellmar T C, Roney D, Lepinski D L
Physiology Department, Armed Forces Radiobiology, Research Institute, Bethesda, MD 20889-5145.
Brain Res. 1992 Jun 26;583(1-2):194-200. doi: 10.1016/s0006-8993(10)80024-1.
Depletion of glutathione (GSH), an intrinsic antioxidant, increases vulnerability to free radical damage in a number of cell systems. This study investigates the role of GSH in limiting electrophysiological damage and/or recovery from free radical exposure in slices of guinea pig hippocampus. Synaptic potentials (PSPs) and population spikes (PSs) were recorded from field CA1. Free radicals were generated from 0.006% peroxide through the Fenton reaction. Analysis of the input-output curves showed that peroxide treatment decreased PSPs and impaired ability of the PSPs to generate PSs as previously reported. Recovery was nearly total within a half hour. Treatment with 5 mM buthionine sulfoximine (BSO) for 2 h depleted hippocampal GSH to 79.2% of control values. The extent of free radical damage was not increased. Recovery, however, was only partial. GSH was further depleted by oxidation with diamide or covalent bonding with dimethyl fumarate (DMF) immediately before and during the peroxide treatment. Neither diamide nor DMF treatment in BSO-incubated tissue enhanced peroxide-induced electrophysiological deficits. Following these treatments, however, tissue showed little recovery from free radical damage. We conclude that glutathione is essential for repair processes in hippocampal neurons exposed to oxidative damage.
谷胱甘肽（GSH）作为一种内源性抗氧化剂，其耗竭会增加许多细胞系统对自由基损伤的易感性。本研究调查了GSH在限制豚鼠海马切片中电生理损伤和/或从自由基暴露中恢复的作用。从CA1区记录突触电位（PSP）和群体峰电位（PS）。通过芬顿反应由0.006%的过氧化物产生自由基。输入-输出曲线分析表明，过氧化物处理会降低PSP，并如先前报道的那样损害PSP产生PS的能力。半小时内恢复几乎完全。用5 mM丁硫氨酸亚砜胺（BSO）处理2小时可使海马GSH耗竭至对照值的79.2%。自由基损伤程度并未增加。然而，恢复只是部分的。在过氧化物处理之前和期间，立即用过二酰胺氧化或与富马酸二甲酯（DMF）共价结合进一步消耗GSH。在经BSO孵育的组织中，过二酰胺和DMF处理均未增强过氧化物诱导的电生理缺陷。然而，经过这些处理后，组织从自由基损伤中的恢复甚微。我们得出结论，谷胱甘肽对于暴露于氧化损伤的海马神经元的修复过程至关重要。
