Gajkowska Barbara, Wojewódzka Urszula, Gajda Joanna
Laboratory of Cell Ultrastructure, Medical Research Centre, Polish Academy of Sciences, 5 Pawiński Street, 02 106 Warsaw, Poland.
J Mol Histol. 2004 Jan;35(1):11-9. doi: 10.1023/b:hijo.0000020900.86650.89.
The cross-talk between endoplasmic reticulum (ER) and mitochondria was investigated during apoptosis in a breast cancer cell line (MCF-7) in culture. The effect of camptothecin, an inducer of apoptosis and a specific inhibitor of topoisomerase I, was investigated by morphological, immunocytochemical and histochemical techniques for electron microscopy. Our ultrastructural morphological data demonstrate alterations in ER configuration and communication with neighbouring mitochondria early after stimulation by camptothecin. Immunoelectron studies have demonstrated that Bax and Bid translocate from cytoplasm to mitochondria where they initiate mitochondrial dysfunction and cytochrome c release. Bax and Bid were also localized in ER and nuclear envelope. Since ER and mitochondria function as intracellular Ca2+ storage, we hypothesize that Bax and Bid are involved in the emptying of ER Ca2+ pool, triggers secondary changes in mitochondrial Ca2+ levels that contribute to cytochrome c release and cell death.
在培养的乳腺癌细胞系（MCF-7）凋亡过程中，对内质网（ER）与线粒体之间的相互作用进行了研究。采用形态学、免疫细胞化学和组织化学电子显微镜技术，研究了凋亡诱导剂喜树碱（一种拓扑异构酶I的特异性抑制剂）的作用。我们的超微结构形态学数据表明，喜树碱刺激后早期内质网结构发生改变，并与相邻线粒体的通讯发生变化。免疫电子研究表明，Bax和Bid从细胞质转移到线粒体，在那里它们引发线粒体功能障碍和细胞色素c释放。Bax和Bid也定位于内质网和核膜。由于内质网和线粒体作为细胞内Ca2+储存库发挥作用，我们推测Bax和Bid参与内质网Ca2+池排空，触发线粒体Ca2+水平的继发性变化，导致细胞色素c释放和细胞死亡。
