Department of Biochemistry, College of Medicine, Soonchunhyang University, Cheonan 330-090, Republic of Korea.
Environ Toxicol Pharmacol. 2011 May;31(3):469-78. doi: 10.1016/j.etap.2011.03.006. Epub 2011 Mar 15.
Cadmium is a well-known toxic metal and occupational exposure to it is associated with lung cancer. In probing the possible non-genotoxic molecular targets of cadmium-induced nasal toxicity, we performed an mRNA differential display analysis for cadmium-treated human nasal septum carcinoma RPMI-2650 cells. Cadmium (≥ 0.5 μM) inhibited the cell proliferation. The intracellular ROS levels were induced by cadmium treatment. In addition, cadmium elicited the AKR1C3 expression. The cadmium-induced increase in AKR1C3 protein levels was suppressed by N-acetylcysteine (NAC) and, to a lesser extent, PI3K inhibitor (Ly294002). Cells pretreated with Ly294002 were more resistant to cadmium toxicity than control. The increase in AKR1C3 protein level was accompanied by an increase in the nuclear transcription factor Nrf2. Overall, our data suggest that cadmium-induced ROS cause up-regulation of AKR1C3 expression, at least partially via the activation of PI3K-related intracellular signaling pathways, and Nrf2 activation, thereby contributing to an adaptive intracellular response to cadmium toxicity.
镉是一种众所周知的有毒金属，职业性暴露于镉会导致肺癌。在探讨镉诱导的鼻毒性的可能非遗传毒性分子靶标时，我们对镉处理的人鼻中隔鳞癌细胞 RPMI-2650 进行了 mRNA 差异显示分析。镉（≥0.5μM）抑制细胞增殖。镉处理诱导细胞内 ROS 水平升高。此外，镉引起 AKR1C3 表达增加。N-乙酰半胱氨酸（NAC）和在较小程度上抑制 PI3K 抑制剂（Ly294002）抑制镉诱导的 AKR1C3 蛋白水平增加。用 Ly294002 预处理的细胞比对照细胞对镉毒性更具抗性。AKR1C3 蛋白水平的增加伴随着核转录因子 Nrf2 的增加。总的来说，我们的数据表明，镉诱导的 ROS 导致 AKR1C3 表达上调，至少部分通过激活 PI3K 相关的细胞内信号通路和 Nrf2 激活，从而有助于对镉毒性的适应性细胞内反应。
