Impairment of antioxidant defenses as a contributor to arsenite-induced cell transformation.
Impairment of antioxidant defenses as a contributor to arsenite-induced cell transformation.
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DOI：
10.1007/s10534-012-9559-1
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发表时间：
2012-10
期刊：
影响因子：
3.5
通讯作者：
Frenkel, Krystyna
中科院分区：
文献类型：
--
作者：
Wu, Jing;Sowinska, Anna;Huang, Xi;Klein, Catherine B.;Pelle, Edward;Frenkel, Krystyna
在暴露 8 周期间以低剂量（0.1–0.5 μM）连续使用亚砷酸盐 (As) 会导致人成骨肉瘤细胞 (HOS) 发生转化。然而，砷转化人类细胞的机制尚不清楚。我们研究了超氧化物歧化酶 1 (SOD1) 和铁蛋白等抗氧化防御蛋白的基因表达和蛋白水平是否发生变化。与对照 HOS 细胞相比，0.1 μM As 诱导更大的细胞增殖并降低抗氧化防御。肿瘤抑制蛋白 p53 的 mRNA 和蛋白水平也均下降。此外，Pig3（p53 诱导基因 3）是 NQO1（NADPH 醌氧化还原酶 1）的同源物，在 As 攻击 8 周后也被下调。用 NQO1 抑制剂二香豆素处理 HOS 细胞，导致 p53 蛋白水平呈剂量依赖性下降，证明了抗氧化酶对 p53 表达以及潜在的下游过程的影响。咖啡酸苯乙酯是一种抗氧化剂，可防止砷诱导的 SOD1、p53 和铁蛋白 mRNA 和蛋白质水平下降。 SOD1、p53 和铁蛋白水平与 As 诱导的细胞增殖呈负相关。总的来说，这些结果强烈表明，抗氧化防御的受损有助于 As 诱导的人类细胞转化，并且 p53 途径参与了该过程。
Arsenite (As) causes transformation of human osteogenic sarcoma cells (HOS) when applied continuously at low doses (0.1–0.5 μM) during 8-weeks of exposure. However, the mechanisms by which As transforms human cells are not known. We investigated whether alterations occurred in gene expression and protein levels of antioxidant defense proteins, such as superoxide dismutase 1 (SOD1) and ferritin. In comparison to control HOS cells, 0.1 μM As induced greater cell proliferation and decreased anti-oxidant defenses. The tumor suppressor protein p53 was also decreased at both mRNA and protein levels. Further, pig3 (p53-induced-gene 3), a homolog of NQO1 (NADPH quinone oxidoreductase 1), was also down-regulated after 8 weeks of As challenge. The treatment of HOS cells with dicumarol, a NQO1 inhibitor, caused a dose-dependent decline in p53 protein levels, proving the effect of an antioxidant enzyme on p53 expression and, potentially, downstream processes. Caffeic acid phenethyl ester, an antioxidant, prevented the As-induced decreases in SOD1, p53, and ferritin mRNA and protein levels. SOD1, p53 and ferritin levels were inversely related to As-induced cell proliferation. Cumulatively, these results strongly suggest that impairment in antioxidant defenses contributes to As-induced human cell transformation and that the p53 pathway is involved in the process.
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影响因子：
4.5
作者：
Erdmann, K;Grosser, N;Schröder, H
通讯作者：
Schröder, H
影响因子：
4.3
作者：
Huang, CS;Ke, QD;Shi, XL
通讯作者：
Shi, XL
DOI：
10.1006/bbrc.1999.1395
发表时间：
1999-09-24
影响因子：
3.1
作者：
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通讯作者：
Menzel, DB
影响因子：
2.8
作者：
Mure, K;Uddin, AN;Rossman, TG
通讯作者：
Rossman, TG
影响因子：
4.8
作者：
Cai, CX;Birk, DE;Linsenmayer, TF
通讯作者：
Linsenmayer, TF