Expression of stress-related genes in a cadmium-resistant A549 human cell line
Expression of stress-related genes in a cadmium-resistant A549 human cell line
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DOI：
10.1080/15287390590925447
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发表时间：
2005-05-14
影响因子：
2.6
通讯作者：
Soleilhavoup, JP
中科院分区：
文献类型：
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作者：
Croute, F;Beau, B;Soleilhavoup, JP
本研究的目的是解释的基础上，镉获得性耐受的A549细胞培养在镉的存在。30天的暴露培养的人肺细胞（A549细胞系），以10 μ M镉先前发现诱导获得性耐药性持续几个星期的文化。此外，这些镉抗性细胞（R细胞）被发现比对照组增殖更快。没有发现R-细胞和对照细胞（S-细胞）之间的基础和镉诱导的金属硫蛋白表达水平的差异。然而，暴露于镉后，细胞谷胱甘肽水平不变的R-细胞，而他们要么增加（在10 μ M镉）或减少（在25 μ M镉）在S-细胞。cDNA阵列分析表明，基因编码（GPx 1）谷胱甘肽过氧化物酶，谷胱甘肽还原酶，过氧化氢酶，超氧化物歧化酶在R-和S-细胞中表达相似，而基因（GPx 2）谷胱甘肽过氧化物酶在R-细胞中过表达。编码应激蛋白的大多数基因类似地表达，除了HSP 27和GRP 94基因，它们在R-细胞中分别表达不足（比率0.5 +/-0.1）和过度（1.8 +/-0.5）。发现急性暴露于Cd触发S细胞中编码伴侣蛋白HSP 90 A、HSP 27、HSP 40、GRP 78、HSP 72和HO-1的基因的上调。在R-细胞中，只有HO-1和HSP 72过表达，但表达水平较低。这表明导致蛋白质错误折叠的Cd相关不利条件在R细胞中降低。很可能R细胞中GPx 2的上调导致这些细胞中更高的抗氧化防御。
This study was designed to explain the basis for Cd-acquired tolerance of A549 cells cultured in the presence of Cd. Thirty-day exposure of cultured human pneumocytes ( A549 cell line) to 10 mu M Cd was previously found to induce an acquired resistance persisting over several weeks of culture. Moreover, these Cd-resistant cells (R-cells) were found to proliferate faster than controls. No difference was found between R-cells and control cells (S-cells) concerning the basal and Cd-induced level of metallothioneins expression. However, after exposure to Cd, cell glutathione levels were unchanged in R-cells while they were either increased ( at 10 mu M Cd) or decreased ( at 25 mu M Cd) in S-cells. cDNA array analysis showed that genes encoding for (GPx1) glutathione peroxidase, glutathione reductase, catalase, and superoxide dismutase were similarly expressed in R- and S-cells, whereas the gene of (GPx2) glutathione peroxidase was overexpressed in R- cells. Most genes encoding stress proteins were similarly expressed, except for HSP27 and GRP94 genes, which were respectively under- ( ratio 0.5 +/- 0.1) and over- (1.8 +/- 0.5) expressed in R- cells. Acute exposure to Cd was found to trigger the upregulation of genes encoding the chaperone proteins HSP90A, HSP27, HSP40, GRP78, HSP72, and HO-1 in S-cells. In R- cells, only HO-1 and HSP72 were overexpressed but at a lower level. This suggests that the Cd-related adverse conditions, leading to protein misfolding, are lowered in R- cells. It is likely that the upregulation of GPx2 in R- cells leads to a higher antioxidant defense in these cells.