Induction of p53-regulated gene expression in human cell lines exposed to the cyanobacterial toxin cylindrospermopsin
Induction of p53-regulated gene expression in human cell lines exposed to the cyanobacterial toxin cylindrospermopsin
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DOI：
10.1080/15287390701434877
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发表时间：
2007-01-01
影响因子：
2.6
通讯作者：
Patel, Bharat
中科院分区：
文献类型：
--
作者：
Bain, Peter;Shaw, Glen;Patel, Bharat
草履虫毒素（CYN）是一种蓝藻毒素，在多种模型中诱导一系列遗传毒性指标。在培养的人皮肤成纤维细胞和人肝细胞癌细胞系HepG2中研究了抑癌蛋白p53在圆柱精子蛋白酶诱导的基因表达中的可能参与。暴露于CYN 6小时后，观察到p53靶基因CDKN 1A、GADD 45 α、BAX和MDM 2的mRNA水平的浓度依赖性增加，表明p53的早期活化。24小时后，这些基因的相对mRNA水平仍然升高。在HepG2衍生的细胞系C3A中，p53蛋白在较长时间暴露后发生积累。数据表明，cylindrospermopsin诱导应激反应，导致p53转录因子的激活。
Cylindrospermopsin (CYN) is a cyanobacterial toxin that induces a range of genotoxic indicators in a variety of models. The possible involvement of the tumor suppressor protein p53 in cylindrospermopsin-induced gene expression was examined in cultured human dermal fibroblasts and the human hepatocellular carcinoma cell line HepG2. After 6 h of exposure to CYN, concentration- dependent increases in mRNA levels were observed for the p53 target genes CDKN1A, GADD45 alpha, BAX, and MDM2, indicating an early activation of p53. After 24 h, relative mRNA levels for these genes remained elevated. Accumulation of p53 protein occurred after longer exposures in the HepG2-derived cell line C3A. Data suggest that cylindrospermopsin induces stress responses that result in the activation of the p53 transcription factor.