Bcl-2 and Hsp27 act at different levels to suppress programmed cell death
Bcl-2 and Hsp27 act at different levels to suppress programmed cell death
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DOI：
10.1038/sj.onc.1201182
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发表时间：
1997-07-17
期刊：
影响因子：
8
通讯作者：
Mignotte, B
中科院分区：
文献类型：
--
作者：
Guenal, I;SidotideFraisse, C;Mignotte, B
细胞凋亡和坏死是两种形态学上不同的细胞死亡形式，可以由常见的刺激诱导，这取决于剂量和细胞类型。本研究比较了癌蛋白Bcl-2和小应激蛋白Hsp 27对这两种类型的细胞死亡的保护作用，我们使用由SV 40大T抗原的tsA 58突变体条件永生化的大鼠胚胎成纤维细胞作为亲本细胞，开发携带可诱导的bcl-2基因的细胞系。2或hsp 27基因。使用两种凋亡刺激：转移到诱导p53介导的凋亡的限制性温度和用低剂量的过氧化氢处理，用高剂量的过氧化氢诱导坏死。虽然Bcl-2和Hsp 27保护这些细胞免于坏死性死亡，但只有Bcl-2似乎能够防止凋亡性死亡，Bcl-2保护不是通过对p53应答基因bax或waf 1的诱导的负面作用介导的，但它减缓了凋亡的至少两个阶段：线粒体膜电位降低和随后的形态学变化，相反，尽管最近已经显示Hsp 27抑制由各种刺激诱导的细胞凋亡，但其过表达对该细胞系统中的细胞凋亡没有影响。还应该注意的是，凋亡刺激（温度变化或过氧化氢处理）诱导Hsp 27而不是Bcl-2积累，这表明在亲本细胞中，Hsp 27可能已经提供了一些保护。然而，综合这些结果表明，Hsp 27以及Bcl-2在几个水平上起作用以抑制细胞死亡，但是它们的保护功能仅部分重叠。
Apoptosis and necrosis, two morphologically distinct forms of cell death, can be induced by common stimuli depending on the doses and the cell type, This study compares the protective effect of oncoprotein Bcl-2 and of the small stress protein Hsp27 on these two types of cell death, We use rat embryo fibroblasts conditionally immortalized by the tsA58 mutant of SV40 large T antigen as parental cells to develop cell lines carrying inducible bcl-2 or hsp27 genes. Two apoptotic stimuli were used: shift to the restrictive temperature that induced p53-mediated apoptosis and treatment with low doses of hydrogen peroxide, Necrosis was induced by high doses of hydrogen peroxide. Although Bcl-2 and Hsp27 protect these cells from necrotic death, only Bcl-2 appears capable of preventing apoptotic death, Bcl-2 protection is not mediated by a negative effect on the induction of the p53 responsive genes bax or waf1 but it slows down at least two stages of apoptosis: decrease of mitochondrial membrane potential and subsequent morphological changes, In contrast, although Hsp27 has been recently shown to inhibit apoptosis induced by various stimuli, its overexpression has no effect on apoptosis in this cell system. It should be also noticed that the apoptotic stimuli (temperature shift or hydrogen peroxide treatment) induce Hsp27, but not Bcl-2 accumulation suggesting that, in parental cells, Hsp27 might already provide some protection, However, taken together these results suggest that Hsp27, as well as Bcl-2, acts at several levels to inhibit cell death, but that their protective functions only partially overlap.