Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 204 George Street, Glasgow G1 1XW, United Kingdom.
Environ Toxicol Pharmacol. 2011 Jul;32(1):54-62. doi: 10.1016/j.etap.2011.03.010. Epub 2011 Mar 15.
Cadmium (Cd) is a toxic heavy metal, and exposure to Cd causes a range of changes within the cell. At high concentrations, Cd causes damage to cells via a range of mechanisms. At low concentrations, Cd can stimulate expression of genes that are part of an adaptive response. In this study, we have used the astrocytoma cell line 1321N1 as a model to investigate the induction of protective enzymes in response to Cd. We have shown that expression of NAD(P)H:quinone oxidoreductase and haem oxygenase enzymes are induced as the protein level by -fold and -fold, and in response to 5 and 10 μM Cd. Levels of NQO1 and HO1 mRNA are also increased by -fold and -fold following 24h exposure to 5 and 10 μM cadmium. An increase in the nuclear accumulation of the transcription factor Nrf2 was also observed following Cd treatment. Through the use of the protein kinase C inhibitor bisindolylmaleimide (VIII) acetate we have demonstrated the involvement PKC in the Nrf2-mediated response of 1321N1 cells to 5-10 μM Cd. We have also shown through the used of 10 μM rottlerin that PKCδ is the isoform responsible for mediating this response.
镉（Cd）是一种有毒重金属，暴露于镉会导致细胞内发生一系列变化。在高浓度下，镉通过多种机制对细胞造成损伤。在低浓度下，镉可以刺激参与适应性反应的基因表达。在这项研究中，我们使用星形细胞瘤细胞系 1321N1 作为模型，研究了细胞对镉的保护性酶的诱导。我们已经表明，NAD（P）H：醌氧化还原酶和血红素加氧酶的表达水平分别增加了 2 倍和 3 倍，并且对 5 和 10 μM 的 Cd 有反应。在暴露于 5 和 10 μM 镉 24 小时后，NQO1 和 HO1 mRNA 的水平也分别增加了 2 倍和 3 倍。在 Cd 处理后，还观察到转录因子 Nrf2 的核积累增加。通过使用蛋白激酶 C 抑制剂双吲哚马来酰亚胺（VIII）乙酸盐，我们已经证明 PKC 参与了 1321N1 细胞对 5-10 μM Cd 的 Nrf2 介导的反应。我们还通过使用 10 μM rottlerin 表明 PKCδ 是介导这种反应的同工型。
