Regulation of nitric oxide synthase induction by iron and glutathione in asbestos-treated human lung epithelial cells.
Regulation of nitric oxide synthase induction by iron and glutathione in asbestos-treated human lung epithelial cells.
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在石棉处理的人肺上皮细胞中铁和谷胱甘肽诱导一氧化氮合酶的调节。
DOI：
10.1006/abbi.1998.0950
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发表时间：
1998
影响因子：
3.9
通讯作者：
Aust,AE
中科院分区：
文献类型：
--
作者：
Park,SH;Aust,AE
用青石棉处理人肺上皮 (A549) 细胞导致诱导型一氧化氮合酶 (iNOS) 的诱导、NO 的产生以及细胞内还原型谷胱甘肽 (GSH) 的急剧减少。 A549 细胞 DNA 中 2'-脱氧-7-氢-8-氧代鸟苷的形成需要从青石棉纤维中动员的铁（按重量计 27% 铁）和 NO 的形成，但 GSH 的减少则不需要。因此，我们研究了GSH和铁在青石棉诱导A549细胞中iNOS的作用。青石棉诱导 iNOS 需要铁。需要五倍量的温石棉（按重量计 3% 铁）才能引起细胞内 GSH 的类似降低和 iNOS 的诱导。在没有石棉的情况下，用丁硫氨酸亚磺酰亚胺 (BSO)（一种 γ-谷氨酰半胱氨酸合成酶抑制剂）或柠檬酸铁铵（FAC）（一种可溶形式的铁）处理不会导致 iNOS 的诱导。然而，当 A549 细胞同时用 BSO 和 FAC 处理时，iNOS 被诱导。 5 mMN-乙酰半胱氨酸的存在阻止了青石棉处理的 A549 细胞中 iNOS 的诱导。这些观察结果表明，iNOS 的诱导是由于细胞内 GSH 的减少和石棉纤维中铁的存在所致。
Treatment of human lung epithelial (A549) cells with crocidolite asbestos resulted in the induction of the inducible form of nitric oxide synthase (iNOS), production of NO, and a dramatic decrease in intracellular reduced glutathione (GSH). Iron, mobilized from the crocidolite fibers (27% iron by weight), and the formation of NO were required for the formation of 2′-deoxy-7-hydro-8-oxoguanosine in the DNA of the A549 cells, but not for the decrease in GSH. Therefore, we investigated the role of GSH and iron in the induction of iNOS in A549 cells by crocidolite. Iron was required for the induction of iNOS by crocidolite. A fivefold higher amount of chrysotile asbestos (3% iron by weight) was required to cause a similar decrease in intracellular GSH and induction of iNOS. In the absence of asbestos, treatment with either buthionine sulfoximine (BSO), an inhibitor of γ-glutamylcysteine synthetase, or ferric ammonium citrate (FAC), a soluble form of iron, did not result in induction of iNOS. However, iNOS was induced when A549 cells were treated simultaneously with BSO and FAC. The presence of 5 mMN-acetylcysteine prevented induction of iNOS in crocidolite-treated A549 cells. These observations suggest that the induction of iNOS resulted from a decrease in intracellular GSH and the presence of iron from the asbestos fibers.