IONICALLY MEDIATED INDUCTION OF MITOGENESIS IN CNS NEURONS
IONICALLY MEDIATED INDUCTION OF MITOGENESIS IN CNS NEURONS
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离子介导的 CNS 神经元有丝分裂诱导
DOI：
10.1111/j.1749-6632.1980.tb15973.x
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发表时间：
1980
影响因子：
5.2
通讯作者：
C. Cone
中科院分区：
文献类型：
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作者：
C. Cone
1971年，本作者根据几项初步研究的结果提出了“关于正常有丝分裂控制和肿瘤发生的基本机制的统一理论”，这些研究表明细胞内离子条件和促有丝分裂活性之间存在功能关系。2这一假说将重点放在细胞内离子等级上（因此，取决于细胞表面的阳离子分配能力）作为控制体细胞中有丝分裂激活的关键决定因素。根据离子电渗和其他膜旁路技术的研究结果，[Na+] i水平尤其被认为具有主要的促有丝分裂重要性，这些技术允许单个阳离子物质选择性沉积到细胞胞质中。特别是[Na+1.这些调查包括细胞系统中的离子（和相关的电跨膜电位）水平的变化进行了测量，在发展过程中的接触抑制有丝分裂在单层培养和以下释放接触抑制的物理和化学手段？和其中调节细胞内ma+] B e1以获得有丝分裂活性的可逆控制的系统。2 3* 虽然电跨膜电位β 1水平通常伴随着ma +]i的变化而变化，但似乎E1变化本身并不显著地参与有丝分裂控制。“在通过降低”a+>而阻止有丝分裂、但E水平没有任何显着变化的条件下进行的观察也支持了这一结论。在假设的最初陈述中，“两个根本性的重要预测（或后果）的论文指出：（1）在有丝分裂过程中，当[Na+]i升高足够长的时间后，CNS神经元等高度不应性细胞可能被诱导启动有丝分裂（2）恶性转化的细胞与同源的no&细胞相比应具有明显升高的[Na+]i，表面上是转化诱导的细胞表面离子分配能力相对于Na+的功能障碍的结果，并且这种持续升高的[Na+]i是恶性增殖的原因。通过细胞内调节诱导CNS神经元有丝分裂的问题
In 1971 the present author proposed a "Unified Theory on the Basic Mechanism of Normal Mitotic Control and Oncogenesis"' based on results from several preliminary studies which suggested a functional relationship between intracellular ionic conditions and mitogenic activity.2 This hypothesis placed central emphasis upon the intracellular ionic hierarchy (and, consequently, upon the cationiepartitioning capabilities of the cell surface) as the key determinant in controlling mitogenesis activation in somatic cells. The [Na+J, level, in particular, was assumed to be of major mitogenic importance on the basis of results from studies with iontophoretic and other membranebypass techniques, which permitted selective deposition of individual cationic species into the cellular cytoplasm2 Subsequent investigations of the general validity of this mitogenesis-control hypothesis for somatic cells have yielded uniformly confirmatory results, particularly of the basic importance of the [Na+l. These investigations have included cell systems in which changes in ionic (and associated electrical transmembrane potential) levels were measured during development of contact-inhibition of mitosis in monolayer cultures and following release from contact-inhibition by both physical and chemical means?' and systems in which the intracellular ma+] b e 1 was modulated to obtain reversible control of mitogenesis activity.2 3* Although the electrical transmembrane potential &, ) level generally changes concomitantly with changes in the wa+]i, it does not appear that the E, change per se is significantly involved in mitogenesis control.' Observations made under conditions wherein mitogenesis was arrested by imposing a decrease in the "a+>, but without any significant change in the E, level, also support this conclusion. In the initial presentation of the hypothesis,' two fundamentally important predictions (or consequences) of the thesis were pointed out: (1) that such highly refractory cells, mitogenically, as CNS neurons might be induced to initiate mitogenesis in response to treatments that produced an adequate elevation of the [Na+]i for a sufficient period (corresponding to a sustained ionic concentrationmediated depolarization of the cell), and (2) that malignantly transformed cells should possess a sipficantly elevated [Na+]i compared to that of the homologous no& cells, ostensibly as a consequence of a transformation-induced dysfunction in the cell-surface ion-partitioning capability with respect to Na+, and that this continuously elevated [Na+]i is the causation of the malignant proliferation. Tbe question of the mitogenic inducibility of CNS neurons via intracellular modulation