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氯化镉对人MDA-MB231乳腺肿瘤细胞某些线粒体相关活性及基因表达的影响。

Effects of cadmium chloride on some mitochondria-related activity and gene expression of human MDA-MB231 breast tumor cells.

作者信息

Cannino Giuseppe, Ferruggia Elisa, Luparello Claudio, Rinaldi Anna Maria

机构信息

Dipartimento di Biologia Cellulare e dello Sviluppo A.Monroy, Università di Palermo, Viale delle Scienze, ed. 16, 90128 Palermo, Italy.

出版信息

J Inorg Biochem. 2008 Aug;102(8):1668-76. doi: 10.1016/j.jinorgbio.2008.04.002. Epub 2008 Apr 22.

DOI:10.1016/j.jinorgbio.2008.04.002
PMID:18534682
Abstract

It was reported that cadmium is able to exert a cytotoxic effect on tumor MDA-MB231 cells, which shows signs of "non-classical" apoptosis and is characterized by drastic changes in gene expression pattern. In this study, we have extended our knowledge of metal-breast cancer cell interactions by analyzing some mitochondria-related aspects of the stress response to CdCl(2) at either 5 or 50 microM 24- or 96-h exposure, by cytochemical, conventional PCR and Northern/Western blot techniques. We demonstrated that (i) no modification of the mitochondrial mass was detectable due to CdCl(2) exposure; (ii) the respiration activity appeared to be increased after 96-h exposures, while the production of reactive oxygen species was significantly induced, as well; (iii) hsp60, hsp70, COXII and COXIV expressions were dependent on the duration of Cd exposure; (iv) a different hsp60 protein distribution was observed in mitochondrial and post-mitochondrial extracts and (v) 96-h exposure induced the over-expression of hsc/hsp70 proteins and, conversely, the down-regulation of cytochrome oxidase subunits II and IV. These observations, in addition to providing more information on the cellular and molecular aspects of the interaction between CdCl(2) and MDA-MB231 breast tumor cells, contribute to the comprehension of the intracellular molecular mechanisms implicated in the regulation of some mitochondrial proteins.

摘要

据报道,镉能够对肿瘤MDA-MB231细胞产生细胞毒性作用,该细胞表现出“非经典”凋亡迹象,并以基因表达模式的剧烈变化为特征。在本研究中,我们通过细胞化学、常规PCR以及Northern/ Western印迹技术,分析了在5或50微摩尔CdCl₂ 24小时或96小时暴露条件下,应激反应中一些与线粒体相关的方面,从而扩展了我们对金属与乳腺癌细胞相互作用的认识。我们证明:(i)由于CdCl₂暴露,未检测到线粒体质量的改变;(ii)96小时暴露后呼吸活性似乎增加,同时活性氧的产生也被显著诱导;(iii)hsp60、hsp70、COXII和COXIV的表达取决于镉暴露的持续时间;(iv)在线粒体提取物和线粒体后提取物中观察到不同的hsp60蛋白分布;(v)96小时暴露诱导hsc/hsp70蛋白的过表达,相反,细胞色素氧化酶亚基II和IV的表达下调。这些观察结果,除了提供更多关于CdCl₂与MDA-MB231乳腺肿瘤细胞相互作用的细胞和分子方面的信息外,还有助于理解参与某些线粒体蛋白调节的细胞内分子机制。

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