Division of Life Science, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong SAR, China.
Biofactors. 2011 Nov-Dec;37(6):439-46. doi: 10.1002/biof.179. Epub 2011 Oct 27.
Tert-butylhydroperoxide (tBHP) challenge caused an initial depletion of cellular reduced glutathione (GSH), which was followed by a gradual restoration of cellular GSH in AML12, H9c2, and differentiated PC12 cells. The time-dependent changes in cellular GSH induced by tBHP were monitored as a measure of GSH recovery capacity (GRC), of which glutathione reductase (GR)-mediated glutathione redox cycling and γ-glutamate cysteine ligase (GCL)-mediated GSH synthesis were found to play an essential role. While glutathione redox cycling sustained the GSH level during the initial tBHP-induced depletion, GSH synthesis restores the GSH level thereafter. The effects of (-)schisandrin B [(-)Sch B] and its analogs (Sch A and Sch C) on GRC were also examined in the cells. (-)Sch B and Sch C, but not Sch A, ameliorated the extent of tBHP-induced GSH depletion, indicative of enhanced glutathione redox cycling. However, the degree of restoration of GSH post-tBHP challenge was not affected or even decreased. Pretreatment with (-)Sch B and Sch C, but not Sch A, protected against oxidant injury in the cells. The (-)Sch B afforded cytoprotection was abolished by N,N'-bis(chloroethyl)-N-nitrosourea pretreatment suggesting the enhancement of glutathione redox cycling is crucially involved in the cytoprotection afforded by (-)Sch B against oxidative stress-induced cell injury.
叔丁基过氧化物（tBHP）挑战导致细胞内还原型谷胱甘肽（GSH）最初耗竭，随后 AML12、H9c2 和分化的 PC12 细胞中的细胞 GSH 逐渐恢复。tBHP 诱导的细胞 GSH 的时间依赖性变化被监测为 GSH 恢复能力（GRC）的度量，其中谷胱甘肽还原酶（GR）介导的谷胱甘肽氧化还原循环和 γ-谷氨酰半胱氨酸连接酶（GCL）介导的 GSH 合成被发现起着至关重要的作用。虽然谷胱甘肽氧化还原循环在初始 tBHP 诱导的耗竭期间维持 GSH 水平，但 GSH 合成此后恢复 GSH 水平。还在细胞中检查了 (-)五味子素 B [(-)Sch B]及其类似物（Sch A 和 Sch C）对 GRC 的影响。(-)Sch B 和 Sch C，但不是 Sch A，减轻了 tBHP 诱导的 GSH 耗竭程度，表明增强了谷胱甘肽氧化还原循环。然而，tBHP 后 GSH 恢复的程度没有受到影响，甚至降低了。(-)Sch B 和 Sch C预处理，但不是 Sch A 预处理，可防止细胞中的氧化损伤。(-)Sch B 提供的细胞保护作用被 N,N'-双（氯乙基）-N-亚硝脲预处理所消除，表明增强谷胱甘肽氧化还原循环在 (-)Sch B 提供的抗氧化应激诱导细胞损伤的细胞保护中起着至关重要的作用。
