Increased cellular levels of spermidine or spermine are required for optimal DNA synthesis in lymphocytes activated by concanavalin A.
Increased cellular levels of spermidine or spermine are required for optimal DNA synthesis in lymphocytes activated by concanavalin A.
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伴刀豆球蛋白 A 激活的淋巴细胞中，需要增加亚精胺或精胺的细胞水平来实现最佳 DNA 合成。
DOI：
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发表时间：
1975
影响因子：
11.1
通讯作者：
D. Morris
中科院分区：
文献类型：
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作者：
R. H. Fillingame;C. M. Jorstad;D. Morris
在伴刀豆球蛋白A诱导转化的淋巴细胞中，多胺、亚精胺和精胺的细胞水平大幅增加。抗白血病药物甲基乙二醛双（鸟苷酰腙）（MGBG）通过抑制S-腺苷甲硫氨酸脱羧酶来阻断这些多胺的合成。先前的结果表明，当细胞在MGBG存在下被激活时，RNA的合成和加工以及蛋白质合成与不存在药物时一样进行。与此相反，[甲基-3H]胸苷掺入DNA和进入有丝分裂的细胞的速度被抑制了60%，在MGBG的存在下。几个实验表明，MGBG通过直接阻断多胺合成而不是通过无关的药理作用抑制细胞增殖：（1）MGBG的抑制作用被外源加入的亚精胺或精胺逆转;（2）MGBG抑制DNA合成显示出与抑制亚精胺和精胺合成相同的剂量-反应曲线;和（3）如果将MGBG加入到已经允许其多胺的最大补体积累的细胞中，则不存在对胸苷掺入的抑制。MGBG处理的培养物和对照培养物同时启动DNA合成，并且通过放射自显影显示相同百分比的标记细胞。因此，似乎在没有多胺的细胞水平增加的情况下，淋巴细胞正常地从G 0进展到G1并进入S期。此外，这些实验表明，通常在快速增殖的真核系统中观察到的亚精胺和精胺水平的增加是DNA复制速率提高所必需的。
There are large increases in cellular levels of the polyamines spermidine and spermine in lymphocytes induced to transform by concanavalin A. The anti-leukemic agent methylglyoxal bis(guanylhydrazone) (MGBG) blocks synthesis of these polyamines by inhibiting S-adenosylmethionine decarboxylase. Previous results showed that when cells are activated in the presence of MGBG the synthesis and processing of RNA, as well as protein synthesis, proceed as in the absence of the drug. In contrast, the incorporation of [methyl-3H]thymidine into DNA and the rate of entry of the cells into mitosis are inhibited by 60% in the presence of MGBG. Several experiments suggest that MGBG inhibits cell proliferation by directly blocking polyamine synthesis and not by an unrelated pharmacological effect: (1) the inhibitory action of MGBG is reversed by exogenously added spermidine or spermine; (2) inhibition of DNA synthesis by MGBG shows the same dose-response curve as does inhibition of spermidine and spermine synthesis; and (3) if MGBG is added to cells which have been allowed to accumulate their maximum complement of polyamines, there is no inhibition of thymidine incorporation. MGBG-treated and control cultures initiate DNA synthesis at the same time and show the same percentage of labeled cells by autoradiography. Therefore, it appears that in the absence of increased cellular levels of polyamines, lymphocytes progress normally from G0 through G1 and into S-phase. Furthermore, these experiments suggest that the increased levels of spermidine and spermine generally seen in rapidly proliferating eukaryotic systems are necessary for enhanced rates of DNA replication.