DIRECT INVOLVEMENT OF P53 IN PROGRAMMED CELL-DEATH OF OLIGODENDROCYTES
DIRECT INVOLVEMENT OF P53 IN PROGRAMMED CELL-DEATH OF OLIGODENDROCYTES
复制标题
DOI：
10.1002/j.1460-2075.1995.tb07097.x
复制
发表时间：
1995-03-15
期刊：
影响因子：
11.4
通讯作者：
SCHWARTZ, M
中科院分区：
文献类型：
--
作者：
EIZENBERG, O;FABERELMAN, A;SCHWARTZ, M
由神经源性转谷氨酰胺酶在体外产生的白介素2的共价二聚体，先前已被证明对成熟的大鼠脑少突胶质细胞具有细胞毒性。在此，我们报道了这种细胞毒作用是通过程序性细胞死亡(细胞凋亡)来实现的，并且p53肿瘤抑制基因直接参与了这一过程。用染色质凝聚和核小体DNA片段化的方法证实了二聚体IL-2处理培养的成熟大鼠脑少突胶质细胞后的细胞凋亡性死亡。细胞凋亡高峰出现在处理后16~24 h，而死亡发生在3~4 h后，内源性P53的定位从胞浆向胞核转移，最早在二聚体IL-2作用15 m in。此外，感染编码C端P53微小蛋白的重组逆转录病毒，以前被证明是内源性野生型P53活性的主要负抑制物，保护这些细胞免受凋亡。
A covalent dimer of interleukin (IL)-2, produced in vitro by the action of a nerve-derived transglutaminase, has been shown previously to be cytotoxic to mature rat brain oligodendrocytes. Here we report that this cytotoxic effect operates via programmed cell death (apoptosis) and that the p53 tumor suppressor gene is involved directly in the process. The apoptotic death of mature rat brain oligodendrocytes in culture following treatment with dimeric IL-2 was demonstrated by chromatin condensation and internucleosomal DNA fragmentation. The peak of apoptosis was observed 16-24 h after treatment, while the commitment to death was already observed after 3-4 h. An involvement of p53 in this process was indicated by the shift in location of constitutively expressed endogenous p53 from the cytoplasm to the nucleus, as early as 15 min after exposure to dimeric IL-2. Moreover, infection with a recombinant retrovirus encoding a C-terminal p53 minoprotein, shown previously to act as a dominant negative inhibitor of endogenous wild-type p53 activity, protected these cells from apoptosis.