Alhonen L, Heikkinen S, Sinervirta R, Halmekytö M, Alakuijala P, Jänne J
A.I. Virtanen Institute and Department of Biochemistry and Biotechnology, University of Kuopio, Finland.
Biochem J. 1996 Mar 1;314 ( Pt 2)(Pt 2):405-8. doi: 10.1042/bj3140405.
We have generated a transgenic mouse line harbouring the human ornithine decarboxylase gene under the control of mouse metallothionein I promoter. Even in the absence of an exposure to heavy metals, ornithine decarboxylase was over-expressed in heart, testis, brain, and especially in liver, of the transgenic animals. An exposure of the transgenic mice to zinc further enhanced the enzyme activity to a level which in liver represented up to 8000-fold increase in comparison with non-transgenic animals. The striking stimulation of liver ornithine decarboxylase activity upon treatment of the transgenic mice with zinc was accompanied by a nearly 150-fold increase in the hepatic putrescine content as compared with similarly treated non-transgenic animals. Even though the liver putrescine concentration reached that of spermidine and spermine in the transgenic animals, the contents of the higher polyamines only transiently increased upon zinc administration and then returned to the basal level. These findings once again indicate that mammalian cells possess extremely powerful regulatory machinery to prevent an over-accumulation of spermidine and spermine in non-dividing cells, and that very high tissue putrescine concentrations can be tolerated, at least for periods of a few days, with seemingly no phenotypic changes.
我们构建了一种转基因小鼠品系，其携带在小鼠金属硫蛋白I启动子控制下的人类鸟氨酸脱羧酶基因。即使在未接触重金属的情况下，转基因动物的心脏、睾丸、大脑，尤其是肝脏中，鸟氨酸脱羧酶也会过度表达。将转基因小鼠暴露于锌中，会进一步增强酶活性，与非转基因动物相比，肝脏中的酶活性提高到高达8000倍的水平。用锌处理转基因小鼠后，肝脏鸟氨酸脱羧酶活性受到显著刺激，同时与同样处理的非转基因动物相比，肝脏腐胺含量增加了近150倍。尽管转基因动物肝脏中的腐胺浓度达到了亚精胺和精胺的浓度，但在给予锌后，较高多胺的含量仅短暂增加，然后又回到基础水平。这些发现再次表明，哺乳动物细胞拥有极其强大的调节机制，以防止在非分裂细胞中亚精胺和精胺过度积累，并且可以耐受非常高的组织腐胺浓度，至少在几天内如此，且似乎没有表型变化。
