Efflux of reduced glutathione after exposure of human lung epithelial cells to crocidolite asbestos
Efflux of reduced glutathione after exposure of human lung epithelial cells to crocidolite asbestos
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DOI：
10.2307/3433546
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发表时间：
1997-09-01
影响因子：
10.4
通讯作者：
Aust, AE
中科院分区：
文献类型：
--
作者：
Golladay, SA;Park, SH;Aust, AE
本研究调查了暴露于鳄鱼石的人肺上皮细胞（A549）谷胱甘肽（GSH）的稳态。A549细胞暴露于3 μ g/cm(2)的青绿石下，细胞内还原性谷胱甘肽减少36%，而谷胱甘肽二硫没有相应的增加。暴露于鳄鱼石24小时后，细胞内丢失的GSH的75%在细胞外培养基中恢复，其中50%以还原形式恢复。由于还原型谷胱甘肽在培养基中的半衰期小于1小时，这表明还原型谷胱甘肽在处理后从细胞中持续释放。GSH的释放似乎不是由非特异性膜损伤引起的，因为在鳄鱼石处理24小时后，负载细胞中没有乳酸脱氢酶或c -14腺嘌呤的同时释放。暴露于鳄鱼石导致s -亚硝基硫醇的形成，但GSH-蛋白质混合二硫化物或GSH偶联物的水平没有增加。A549细胞暴露于青橄榄石24小时后，γ - gcs活性降低47%，而谷胱甘肽还原酶、谷胱甘肽过氧化物酶、谷胱甘肽s -转移酶或葡萄糖-6-磷酸脱氢酶活性不变。用铁螯合剂去铁胺B预处理的红石处理细胞，与用未修饰的红石处理细胞相比，细胞内GSH消耗和外排水平相同，γ - gcs活性下降相同，这表明铁催化反应不是造成GSH消耗的原因。
This study investigated glutathione (GSH) homeostasis in human lung epithelial cells (A549) exposed to crocidolite. Exposure of A549 cells to 3 mu g/cm(2) crocidolite resulted in a decrease in intracellular reduced glutathione by 36% without a corresponding increase in GSH disulfide. After a 24-hr exposure to crocidolite, 75% of the intracellular GSH lost was recovered in the extracellular medium, of which 50% was in reduced form. Since the half-life of reduced GSH in culture medium was less than 1 hr, this suggests that reduced GSH was released continuously from the cells after treatment. The release of GSH did not appear to result from nonspecific membrane damage, as there was no concomitant release of lactate dehydrogenase or C-14-adenine from loaded cells after crocidolite treatment for 24 hr. Crocidolite exposure resulted in the formation of S-nitrosothiols but no increase in the level of GSH-protein mixed disulfides or GSH conjugates. Exposure of A549 cells to crocidolite for 24 hr decreased gamma glutamylcysteine synthetase (gamma-GCS) activity by 47% without changes in the activities of GSH reductase, GSH peroxidase, GSH S-transferase, or glucose-6-phosphate dehydrogenase. Treatment of cells with crocidolite pretreated with the iron chelator desferrioxamine B resulted in the same level of intracellular GSH depletion and efflux and the same decrease in gamma-GCS activity as treatment with unmodified crocidolite, which suggests that iron-catalyzed reactions were not responsible for the GSH depletion.