Svensson F, Kockum I, Persson L
Department of Physiology and Biophysics, University of Lund, Sweden.
Mol Cell Biochem. 1993 Jul 21;124(2):141-7. doi: 10.1007/BF00929206.
The polyamines are cell constituents essential for growth and differentiation. S-Adenosylmethionine decarboxylase (AdoMetDC) catalyzes a key step in the polyamine biosynthetic pathway. Methylglyoxal bis(guanylhydrazone) (MGBG) is an anti-leukemic agent with a strong inhibitory effect against AdoMetDC. However, the lack of specificity limits the usefulness of MGBG. In the present report we have used an analog of MGBG, diethylglyoxal bis(guanylhydrazone) (DEGBG), with a much greater specificity and potency against AdoMetDC, to investigate the effects of AdoMetDC inhibition on cell proliferation and polyamine metabolism in mouse L1210 leukemia cells. DEGBG was shown to effectively inhibit AdoMetDC activity in exponentially growing L1210 cells. The inhibition of AdoMetDC was reflected in a marked decrease in the cellular concentrations of spermidine and spermine. The concentration of putrescine, on the other hand, was greatly increased. Treatment with DEGBG resulted in a compensatory increase in the synthesis of AdoMetDC demonstrating an efficient feedback control. Cells seeded in the presence of DEGBG ceased to grow after a lag period of 1-2 days, indicating that the cells contained an excess of polyamines which were sufficient for one or two cell cycles in the absence of polyamine synthesis. The present results indicate that analogs of MGBG, having a greater specificity against AdoMetDC, might be valuable for studies concerning polyamines and cell proliferation.
多胺是细胞生长和分化所必需的成分。S-腺苷甲硫氨酸脱羧酶（AdoMetDC）催化多胺生物合成途径中的关键一步。甲基乙二醛双（脒腙）（MGBG）是一种抗白血病药物，对AdoMetDC具有很强的抑制作用。然而，缺乏特异性限制了MGBG的实用性。在本报告中，我们使用了一种MGBG类似物，二乙基乙二醛双（脒腙）（DEGBG），它对AdoMetDC具有更高的特异性和效力，以研究抑制AdoMetDC对小鼠L1210白血病细胞增殖和多胺代谢的影响。结果表明，DEGBG能有效抑制指数生长期L1210细胞中的AdoMetDC活性。AdoMetDC的抑制表现为亚精胺和精胺细胞浓度显著降低。另一方面，腐胺的浓度则大大增加。用DEGBG处理导致AdoMetDC合成的代偿性增加，表明存在有效的反馈控制。在DEGBG存在的情况下接种的细胞在1 - 2天的延迟期后停止生长，这表明细胞含有过量的多胺，在没有多胺合成的情况下足以支持一到两个细胞周期。目前的结果表明，对AdoMetDC具有更高特异性的MGBG类似物可能对多胺和细胞增殖的研究有价值。
