GLUTATHIONE EXPORT BY HUMAN LYMPHOID-CELLS - DEPLETION OF GLUTATHIONE BY INHIBITION OF ITS SYNTHESIS DECREASES EXPORT AND INCREASES SENSITIVITY TO IRRADIATION
GLUTATHIONE EXPORT BY HUMAN LYMPHOID-CELLS - DEPLETION OF GLUTATHIONE BY INHIBITION OF ITS SYNTHESIS DECREASES EXPORT AND INCREASES SENSITIVITY TO IRRADIATION
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DOI：
10.1073/pnas.78.12.7492
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发表时间：
1981-01-01
期刊：
影响因子：
--
通讯作者：
MEISTER, A
中科院分区：
文献类型：
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作者：
DETHMERS, JK;MEISTER, A
谷胱甘肽（以GSH的形式）以与细胞内谷胱甘肽水平成比例的速率从培养的人淋巴细胞中转运出来。γ-谷氨酰胺的有效选择性抑制剂丁硫酰亚胺对谷胱甘肽合成的抑制谷氨酰半胱氨酸合成酶导致细胞内谷胱甘肽指数下降，其中大部分出现在细胞外，表明谷胱甘肽周转与其输出有关。尽管含0.09 mM谷胱甘肽的细胞（对照组的4%）的存活率为85%，但进一步降低与存活率的显著丧失相关。具有4-5%对照谷胱甘肽水平的细胞比对照细胞对γ-谷氨酰胺的作用敏感得多。辐射和5.5“-二硫代双（2-硝基苯甲酸酯）。通过使用丁硫克百威亚砜亚胺消耗谷胱甘肽具有优于其他试剂（如二酰胺、其他氧化剂和马来酸二乙酯，其影响其他细胞组分并可能增加谷胱甘肽二硫化物水平）的优势，并且在使细胞对辐射效应和通过涉及谷胱甘肽的反应解毒的治疗剂敏感方面具有潜在的有用性。
Glutathione (in the form of GSH) is transported out of cultured human lymphoid cells at rates proportional to the intracelluar glutathione levels. Inhibition of glutathione synthesis by buthionine sulfoximine, a potent selective inhibitor of .gamma.-glutamylcysteine synthetase, leads to exponential decrease in intracellular glutathione, a large fraction of which appears extracellularly, indicating that glutathione turnover is associated with its export. Although cells with 0.09 mM glutathione (4% of controls) were 85% viable, further decrease was associated with marked loss of viability. Cells with 4-5% of control glutathione levels were much more sensitive than control cells to the effects of .gamma.-radiation and of 5.5''-dithiobis(2-nitrobenzoate). Depletion of glutathione by use of buthionine sulfoximine has advantages over other reagents (such as diamide, other oxidizing agents and diethylmaleate, which affect other cellular components and may increase glutathione disulfide levels) and has potential usefulness in sensitizing cells to the effects of radiation and to therapeutic agents that are detoxified by reactions involving glutathione.