Marty C, Mori G, Sabini L, Rivarola V
Facultad de Ciencias Exactas, Físico-Químicas y Naturales, Universidad Nacional de Río Cuarto, Córdoba, Argentina.
Biocell. 2000 Apr;24(1):49-52.
DFMO is an irreversible inhibitor of ornithine decarboxilase (ODC), the key enzyme in mammalian polyamine biosynthesis. The goal of this study was to determine the effects of DFMO on the expression of cyclin A at different stages of the cell cycle of Hep-2 cells. The cell cycle analysis, done by measuring the incorporation of thymidine in the cell DNA, revealed that DFMO produced a lower and constant level of that incorporation; this effect is probably due to the incapacity of the cells to culminate the phase S of the cell cycle. The expression of cyclin A increased in the phases S and G2 in control cells, almost disappearing in phase M. However, in DFMO treated cultures, the expression of cyclin A was increased in M and this effect remained still after 48 h treatment. We conclude that polyamines could exert an effect on the cyclin destruction mechanism, and the depletion caused by DFMO would alter this mechanism.
二氟甲基鸟氨酸(DFMO)是鸟氨酸脱羧酶(ODC)的不可逆抑制剂,ODC是哺乳动物多胺生物合成中的关键酶。本研究的目的是确定DFMO对Hep-2细胞细胞周期不同阶段细胞周期蛋白A表达的影响。通过测量细胞DNA中胸苷的掺入进行的细胞周期分析表明,DFMO使该掺入水平降低且保持恒定;这种效应可能是由于细胞无法完成细胞周期的S期。在对照细胞中,细胞周期蛋白A的表达在S期和G2期增加,在M期几乎消失。然而,在DFMO处理的培养物中,细胞周期蛋白A的表达在M期增加,并且在处理48小时后这种效应仍然存在。我们得出结论,多胺可能对细胞周期蛋白破坏机制产生影响,而DFMO导致的多胺耗竭会改变这种机制。