Chatterjee Soumya, Kundu Subhadip, Bhattacharyya Arindam
Department of Environmental Science, University of Kalyani, West Bengal 741235, India.
Toxicol Lett. 2008 Mar 15;177(2):83-9. doi: 10.1016/j.toxlet.2007.12.010. Epub 2007 Dec 28.
Cadmium is the major component of polluted environment which can be fatal by mechanisms that are not fully clear. Our study indicates immunosupression may be one of the reason for that. It is well known that cadmium (Cd) has toxic and carcinogenic effects in rhondents and humans, but the effects of cadmium on apoptosis are still not clear. Although some studies have shown that cadmium has apoptotic potential, other studies have shown that cadmium can be anti-apoptotic. In the present study, we aimed to determine the mode of cell death and its mechanism in Swiss albino mice splenocyte by cadmium for its toxic effects. To identify the nature of cell death, our result signifies apoptotic mode of killing. In search of the mechanism behind it we found that cadmium increased cell death and lowered the survival of the host in a dose dependent manner. In search of the reason we found increased expression of the pro-apoptotic proteins p53 in splenic lymphocytes. Here we showed that cadmium induced p53-dependent apoptosis through cooperation between Bcl-xl down regulation without changing the Bcl-2 and Bax expression, the common target of p53. The down regulation of Bcl-xl strongly indicating mitochondrial involvement in apoptosis. It is confirmed by the release of cytochrome c and activation of caspase-3. All of these findings establish an important role of p53 and mitochondrial function in cadmium induced toxic environment in the host.
镉是污染环境的主要成分，其致死机制尚不完全清楚。我们的研究表明免疫抑制可能是原因之一。众所周知，镉（Cd）对啮齿动物和人类具有毒性和致癌作用，但镉对细胞凋亡的影响仍不清楚。尽管一些研究表明镉具有诱导细胞凋亡的潜力，但其他研究表明镉可以抗细胞凋亡。在本研究中，我们旨在确定镉对瑞士白化小鼠脾细胞的细胞死亡模式及其机制，以了解其毒性作用。为了确定细胞死亡的性质，我们的结果表明是凋亡性杀伤模式。在寻找其背后的机制时，我们发现镉以剂量依赖的方式增加细胞死亡并降低宿主的存活率。在寻找原因时，我们发现脾淋巴细胞中促凋亡蛋白p53的表达增加。在这里，我们表明镉通过下调Bcl-xl而不改变p53的共同靶点Bcl-2和Bax的表达之间的协同作用诱导p53依赖性细胞凋亡。Bcl-xl的下调强烈表明线粒体参与了细胞凋亡。细胞色素c的释放和caspase-3的激活证实了这一点。所有这些发现确立了p53和线粒体功能在镉诱导的宿主毒性环境中的重要作用。
