Laun Peter, Ramachandran Lakshmi, Jarolim Stefanie, Herker Eva, Liang Ping, Wang Jianxin, Weinberger Martin, Burhans Debra T, Suter Bernhard, Madeo Frank, Burhans William C, Breitenbach Michael
Department of Cell Biology, Salzburg University, Hellbrunnerstr. 34, Austria.
FEMS Yeast Res. 2005 Dec;5(12):1261-72. doi: 10.1016/j.femsyr.2005.07.006. Epub 2005 Aug 31.
In this paper, we present the results of global transcript analysis by the microarray technique of senescent and apoptotic yeast cells. We compared young daughter and old mother cells isolated by elutriation centrifugation, and non-apoptotic and apoptotic cells induced either by a temperature shift of the cdc48(S565G) temperature-sensitive mutant or of the orc2-1 temperature-sensitive mutant. The majority of all genes found to be differentially regulated in these three physiological situations was upregulated, indicating that a cellular death process was initiated rather than an unspecific shut-down of gene expression due to immediate killing. The functional classes of genes upregulated in all three conditions were largely the same, although individual genes were in many cases not identical. The largest group of genes involved were nuclear genes coding for mitochondrial components or functions, which is understandable given the fact that apoptosis can be triggered by mitochondrially generated oxygen radicals and that mitochondria play an important role in the execution of apoptosis. Other functional classes consisted of genes involved in DNA damage response, in cell cycle regulation and checkpoints, in DNA repair, and in membrane lipid and cell wall synthesis. These functional classes represent the response of the cell to the known cellular insults, which occur during aging and apoptosis. As we have shown previously, final-stage senescent yeast mother cells (of the wild-type) are apoptotic.
在本文中,我们展示了通过微阵列技术对衰老和凋亡酵母细胞进行全局转录分析的结果。我们比较了通过淘析离心分离出的年轻子代细胞和年老母细胞,以及由cdc48(S565G)温度敏感突变体或orc2 - 1温度敏感突变体的温度变化诱导产生的非凋亡细胞和凋亡细胞。在这三种生理情况下发现的大多数差异调节基因都上调了,这表明启动了一个细胞死亡过程,而不是由于直接杀伤导致基因表达的非特异性关闭。在所有三种情况下上调的基因功能类别基本相同,尽管在许多情况下个别基因并不相同。涉及的最大一组基因是编码线粒体成分或功能的核基因,鉴于凋亡可由线粒体产生的氧自由基触发且线粒体在凋亡执行中起重要作用,这是可以理解的。其他功能类别包括参与DNA损伤反应、细胞周期调控和检查点、DNA修复以及膜脂和细胞壁合成的基因。这些功能类别代表了细胞对在衰老和凋亡过程中发生的已知细胞损伤的反应。正如我们之前所表明的,(野生型)最终阶段的衰老酵母母细胞是凋亡的。