Hayashi S, Kameji T, Fujita K, Murakami Y, Kanamoto R, Utsunomiya K, Matsufuji S, Takiguchi M, Mori M, Tatibana M
Adv Enzyme Regul. 1985;23:311-29. doi: 10.1016/0065-2571(85)90054-8.
A single injection of thioacetamide into starved rats induced a 40- to 100-fold increase in hepatic ODC activity. However, immunotitratable ODC protein increased by only 5-fold because of the presence of significant amounts of inactive ODC protein in the liver of untreated starved rats. Polysomal ODC-mRNA activity also increased only 5-fold, a significant amount being present in control liver. Furthermore, the peak of polysomal ODC-mRNA activity preceded that of ODC activity or ODC protein by several hours. These results indicate that the enzyme induction is due not only to increase in polysomal ODC-mRNA activity, but also to some translational and/or post-translational regulation. Exogenously administered diamines or polyamines cause rapid decay of ODC activity and induce antizyme that binds to ODC and inactivates it. Another protein factor, antizyme inhibitor, was found in the liver of thioacetamide-treated or protein-fed rats. Antizyme inhibitor binds to antizyme and reactivates ODC in the ODC-antizyme complex. A small, but significant, amount of antizyme was found in the liver of starved rats. Only small amounts of ODC-antizyme complex were detected in rat liver and cultured hepatocytes, even during the period of rapid ODC decay caused by exogenously added diamines. On the other hand, the complex was present in HTC cells and more especially in ODC-stabilized HMOA cells, even under physiological conditions. On addition of 10(-2) M putrescine, the amount of complex first increased and then decreased in both types of cells. Decay of total ODC activity (free plus complexed ODC) was more rapid with putrescine than with cycloheximide. These results suggest that antizyme plays an essential role in the degradation of ODC by a catalytic effect both in the presence and absence of exogenous putrescine and that antizyme inhibitor stabilizes ODC by removing antizyme.
向饥饿大鼠单次注射硫代乙酰胺可使肝脏鸟氨酸脱羧酶（ODC）活性增加40至100倍。然而，由于未处理的饥饿大鼠肝脏中存在大量无活性的ODC蛋白，免疫滴定法检测到的ODC蛋白仅增加了5倍。多聚核糖体ODC - mRNA活性也仅增加了5倍，在对照肝脏中就存在相当数量的该活性。此外，多聚核糖体ODC - mRNA活性的峰值比ODC活性或ODC蛋白的峰值提前数小时出现。这些结果表明，酶的诱导不仅是由于多聚核糖体ODC - mRNA活性的增加，还归因于一些翻译和/或翻译后调控。外源性给予二胺或多胺会导致ODC活性迅速衰减，并诱导与ODC结合并使其失活的抗酶。在硫代乙酰胺处理的大鼠或蛋白质喂养的大鼠肝脏中发现了另一种蛋白质因子，即抗酶抑制剂。抗酶抑制剂与抗酶结合并使ODC - 抗酶复合物中的ODC重新激活。在饥饿大鼠的肝脏中发现了少量但显著的抗酶。即使在由外源性添加二胺导致ODC迅速衰减的期间，在大鼠肝脏和培养的肝细胞中也仅检测到少量的ODC - 抗酶复合物。另一方面，即使在生理条件下，该复合物也存在于HTC细胞中，更特别地存在于ODC稳定的HMOA细胞中。加入10⁻² M腐胺后，两种细胞类型中复合物的量先增加后减少。腐胺导致的总ODC活性（游离ODC加上复合ODC）的衰减比环己酰亚胺更快。这些结果表明，无论是否存在外源性腐胺，抗酶在ODC降解中都通过催化作用发挥重要作用，并且抗酶抑制剂通过去除抗酶来稳定ODC。
