O'Connor E, Devesa A, García C, Puertes I R, Pellín A, Viña J R
Departamento de Bioquímica-Biología Molecular, Facultad de Medicina y Odontología, Universitat de Valencia, Spain.
Brain Res. 1995 May 22;680(1-2):157-63. doi: 10.1016/0006-8993(95)00257-q.
We have studied the optimal conditions to maintain the astrocyte GSH levels under normal and oxidative stress conditions. The rate of GSH synthesis from L-methionine was statistically lower than from L-cystine or N-acetyl-cysteine in astrocytes treated with diethyl-maleate, which is a substrate of GSH S-transferases. This is in accordance with the fact that cystathionase activity was not detectable. The transport of L-cystine mediated by the Na(+)-independent system Xc- is the limiting step in GSH synthesis in astrocytes. Incubation with tert-butyl hydroperoxide (t-booH) reduced GSH concentration in astrocytes. This reduction was ameliorated in part by the addition of ascorbate or dehydroascorbate. When L-cystine and ascorbate were added together to the t-booH-treated astrocytes, the GSH concentration was indistinguishable from controls. Electron micrographs of astrocytes treated with t-booH showed an increased number of vacuoles and mitochondrial swelling. This was prevented by ascorbate and dehydroascorbate. The physiological implications of the availability of GSH precursors and ascorbate in the maintenance of GSH in astrocytes are discussed.
我们研究了在正常和氧化应激条件下维持星形胶质细胞谷胱甘肽（GSH）水平的最佳条件。在用马来酸二乙酯（GSH S-转移酶的一种底物）处理的星形胶质细胞中，由L-蛋氨酸合成GSH的速率在统计学上低于由L-胱氨酸或N-乙酰半胱氨酸合成的速率。这与无法检测到胱硫醚酶活性的事实相符。由不依赖Na(+)的系统Xc-介导的L-胱氨酸转运是星形胶质细胞中GSH合成的限速步骤。用过氧化叔丁基（t-booH）孵育会降低星形胶质细胞中的GSH浓度。添加抗坏血酸或脱氢抗坏血酸可部分改善这种降低。当将L-胱氨酸和抗坏血酸一起添加到用t-booH处理的星形胶质细胞中时，GSH浓度与对照无明显差异。用t-booH处理的星形胶质细胞的电子显微镜照片显示空泡数量增加和线粒体肿胀。抗坏血酸和脱氢抗坏血酸可防止这种情况发生。本文讨论了GSH前体和抗坏血酸的可用性在维持星形胶质细胞中GSH方面的生理意义。
