Proliferation and death of conditionally immortalized neural cells from murine neocortex: p53 alters the ability of neuron-like cells to re-enter the cell cycle.
Proliferation and death of conditionally immortalized neural cells from murine neocortex: p53 alters the ability of neuron-like cells to re-enter the cell cycle.
复制标题
小鼠新皮质条件永生化神经细胞的增殖和死亡：p53 改变神经元样细胞重新进入细胞周期的能力。
DOI：
10.1016/s0006-8993(02)04119-7
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发表时间：
2003
期刊：
影响因子：
2.9
通讯作者：
Wyllie,AH
中科院分区：
文献类型：
--
作者：
Miller,MW;Peter,A;Wharton,SB;Wyllie,AH
神经元的独特之处在于它们通常被认为是永久性的有丝分裂后细胞。癌蛋白p53是神经元发育，尤其是细胞增殖和神经元死亡的关键调节因子。我们假设p53维持分化神经元的有丝分裂后特征。为了验证这一假设，产生了条件永生的皮层细胞系。从双转基因小鼠的新皮层中获得细胞群，这些细胞不含p53并表达对温度敏感的SV40大T抗原。在允许的温度（32℃）下，细胞继续增殖，并且大多数表达巢蛋白和与胶质细胞相关的蛋白。在非允许温度（39°C）下，细胞表达与分化神经元相关的细胞骨架蛋白，如微管相关蛋白2和神经丝200。在允许条件下，p53+/−和p53 - /−细胞表现出相似的循环行为；细胞周期为13 ~ 15h， 85%的细胞处于活跃循环状态。在非允许条件下，大多数p53+/ -细胞停止分裂，而p53 - / -细胞继续增殖。细胞的存活率也有所不同。在非允许条件下，许多p53+/ -细胞在用神经毒素（乙醇，400 mg/dl）处理后死亡，而p53 - / -细胞没有死亡。在重新引入允许条件后，两种细胞系都表达了神经元样特征，但只有p53 - / -细胞保留了它们的循环能力。因此，p53介导的活性似乎参与了神经元样细胞的增殖、存活和有丝分裂后的性质。
Neurons are distinctive in that they are generally considered to be permanently post-mitotic cells. The oncoprotein p53 is a key regulator in neuronal development, notably in cell proliferation and neuronal death. We hypothesize that p53 maintains the post-mitotic characteristic of differentiated neurons. New lines of conditionally immortalized cortical cells were generated to test this hypothesis. Populations of cells were obtained from the neocortices of dual transgenic mice that were null for p53 and expressed a temperature-sensitive SV40 large T antigen. At a permissive temperature (32°C), the cells continued to proliferate and most expressed nestin and proteins associated with glia. At a non-permissive temperature (39°C), the cells expressed cytoskeletal proteins associated with differentiated neurons such as microtubule associated protein 2 and neurofilament 200. Under permissive conditions, both p53+/−and p53−/−cells exhibited similar cycling behaviors; the length of the cell cycle was 13–15 h and >85% of the cells were actively cycling. In non-permissive conditions, most p53+/−cells stopped dividing, whereas the p53−/−cells continued to proliferate. The survival of the cells also differed. In the non-permissive conditions, many p53+/−cells died following treatment with a neurotoxin (ethanol, 400 mg/dl), whereas the p53−/−cells did not. After re-introduction to the permissive conditions, both cell lines expressed neuron-like characteristics, but only the p53−/−cells retained their ability to cycle. Therefore, p53-mediated activities appear to be involved in the proliferation, survival, and post-mitotic nature of neuron-like cells.