EFFECTS OF SODIUM ARSENITE ON THE CYTOSKELETON AND CELLULAR GLUTATHIONE LEVELS IN CULTURED-CELLS
EFFECTS OF SODIUM ARSENITE ON THE CYTOSKELETON AND CELLULAR GLUTATHIONE LEVELS IN CULTURED-CELLS
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DOI：
10.1016/0041-008x(92)90105-2
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发表时间：
1992-05-01
影响因子：
3.8
通讯作者：
CHOU, IN
中科院分区：
文献类型：
--
作者：
LI, WD;CHOU, IN
在Swiss 3 T3小鼠细胞中研究了As 3+（NaAsO 2）对微管和微丝组织、细胞骨架蛋白合成、细胞骨架和细胞溶质（可溶性）蛋白巯基以及细胞谷胱甘肽（GSH）水平的影响。细胞暴露于2.5 μ mAs ~（3+）16小时后，细胞明显收缩，肌动蛋白丝粗索消失。然而，细胞仍保留许多较细的微丝以无序的方式分布。微管组织相对不受干扰。在较高剂量（≥20 μm）下，As ~（3+）处理引起微管的严重丢失，剩余的致密的微丝在核周区形成模糊的簇。用As 3+处理细胞也诱导细胞骨架蛋白合成的剂量依赖性抑制。此外，As 3+暴露增强细胞GSH合成，因为As 3+处理的细胞中升高的细胞GSH含量可以通过丁硫丙磺酰亚胺（GSH生物合成所需的γ-谷氨酰半胱氨酸合成酶抑制剂）处理而消除。正如所确定的N-[3 H]-乙基马来酰亚胺结合试验，砷3+曝光也增加了蛋白质巯基的量在细胞骨架和胞质蛋白组分。此外，更大的增加蛋白质巯基发生在细胞骨架馏分比可溶性馏分。这些结果表明，细胞骨架可能是一个细胞损伤的目标，由砷暴露。As 3+诱导的细胞GSH含量升高可能提供了一种保护机制，以防止这种金属损伤的进一步损伤。
The effects of As3+(NaAsO2) on the microtubule and microfilament organization, cytoskeletal protein synthesis, cytoskeletal and cytosolic (soluble) protein sulfhydryls, and cellular glutathione (GSH) levels were examined in Swiss 3T3 mouse cells. Exposure of cells to 2.5 μm As3+for 16 hr resulted in apparent cell retraction and loss of thick cables of actin filaments. However, the cells still retained numerous thinner microfilaments distributed in a disorganized manner. Microtubule organization was relatively undisturbed. At higher doses (≥20 μm), As3+treatment caused a severe loss of microtubules and the remaining dense finer actin filaments formed smearing clusters in perinuclear areas. Treatment of cells with As3+also induced a dose-dependent inhibition of cytoskeletal protein synthesis. Furthermore, As3+exposure enhanced cellular GSH synthesis since the elevated cellular GSH content in As3+-treated cells could be abolished by treatment with buthionine sulfoximine, an inhibitor of γ-glutamylcysteine synthetase required for GSH biosynthesis. As determined by the N-[3H]-ethylmaleimide binding assay, As3+exposure also increased the amount of protein sulfhydryls in both the cytoskeletal and the cytosolic protein fractions. Moreover, a greater increase in protein sulfhydryls occurred in the cytoskeletal fraction than in the soluble fraction. These results indicate that the cytoskeleton could be a cellular target for injury by As3+exposure. The elevated cellular GSH content induced by As3+could provide a protective mechanism against further injury from this metal insult.