Loss of cell cycle controls in apoptotic lymphoblasts of the bursa of Fabricius.
Loss of cell cycle controls in apoptotic lymphoblasts of the bursa of Fabricius.
复制标题
法氏囊凋亡淋巴母细胞失去细胞周期控制。
DOI：
10.1091/mbc.5.7.763
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发表时间：
1994
影响因子：
3.3
通讯作者：
Thomas,SJ
中科院分区：
文献类型：
--
作者：
Neiman,PE;Blish,C;Heydt,C;Loring,G;Thomas,SJ
法氏鸡法氏囊正常胚胎滤泡的淋巴母细胞在受到伽马射线照射或短期培养过程中细胞-细胞接触被机械分散破坏时，会发生迅速的凋亡。我们以前已经观察到，v-myc的过度表达使癌前法氏囊淋巴母细胞对诱导细胞死亡敏感，而对诱导细胞死亡的抵抗是在肿瘤进展过程中获得的。在这项研究中，我们观察到在弥散诱导细胞凋亡后的第一小时内，绝大多数淋巴母细胞群体中的DNA发生了广泛的降解。矛盾的是，这些细胞继续进入S期，大部分DNA断裂和死亡发生在S期细胞中(即DNA含量大于2C而低于4CDNA的细胞)。我们通过确定单个细胞中核周期蛋白A的检测与DNA断裂的检测相对应，确认了凋亡细胞的S时相状态。在弥散诱导的DNA切割过程中，细胞周期蛋白E、依赖于细胞周期蛋白E的H1组蛋白激酶和P53蛋白的水平保持不变。伽玛射线既不能抑制细胞周期进展，也不能提高分散的法氏囊淋巴母细胞中的P53水平。在完整的法氏囊泡中，低剂量的伽马射线诱导P53蛋白表达，而较高剂量的细胞凋亡诱导蛋白表达不能诱导P53蛋白表达，也不能阻止G1期向S期的进展。这些结果表明，当诱导法氏囊淋巴母细胞凋亡时，正常的DNA损伤诱导的细胞周期检查点控制被丢失或被覆盖。
Lymphoblasts of the normal embryonic follicles of the chicken bursa of Fabricius undergo rapid apoptosis when exposed to gamma-radiation or when cell-cell contacts are disrupted by mechanical dispersion in short term culture. We have observed previously that overexpression of v-myc sensitizes preneoplastic bursal lymphoblasts to induction of cell death, whereas resistance to induced cell death is acquired during progression to neoplasia. In this study we observed extensive DNA degradation in the large majority of the lymphoblast population within the first hour after dispersion-induced apoptosis. Paradoxically these cells continued to progress into S-phase with the bulk of DNA cleavage and death occurring in S-phase cells (i.e., in cells with more than 2C and less than 4C DNA content). We confirmed the S phase status of apoptotic cells by determining that detection of nuclear cyclin A in individual cells also corresponded with detection of DNA breakage. Levels of cyclin E, cyclin E-dependent H1 histone kinase, and p53 proteins were maintained during dispersion-induced DNA cleavage. gamma-radiation failed either to inhibit cell cycle progression or to raise p53 levels in dispersed bursal lymphoblasts. In intact bursal follicles low doses of gamma-radiation induced p53 whereas higher, apoptosis-inducing doses failed to induce p53 or prevent G1 to S-phase progression. These results suggest that normal DNA damage-induced cell cycle checkpoint controls are lost or overridden when apoptosis is induced in bursal lymphoblasts.