Antizyme protects against abnormal accumulation and toxicity of polyamines in ornithine decarboxylase-overproducing cells.
Antizyme protects against abnormal accumulation and toxicity of polyamines in ornithine decarboxylase-overproducing cells.
复制标题
抗酶可防止鸟氨酸脱羧酶过量产生的细胞中多胺的异常积累和毒性。
DOI：
10.1073/pnas.91.19.8930
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发表时间：
1994
影响因子：
11.1
通讯作者：
K. Igarashi
中科院分区：
文献类型：
--
作者：
Toshikazu Suzuki;Yong He;K. Kashiwagi;Y. Murakami;S. Hayashi;K. Igarashi
暴露于微摩尔水平的精胺或亚精胺的鸟氨酸脱羧酶（ODC; L-鸟氨酸羧基裂解酶，EC 4.1.1.17）-过度产生小鼠FM 3A细胞引起多胺的异常积累和毒性。这显然是由于多胺转运的负反馈控制在ODC过量生产细胞的效率低下。由于抗酶是迄今为止发现的唯一能与ODC相互作用的蛋白质，游离抗酶的耗竭被认为是多胺异常积累的原因。因此，用具有在糖皮质激素诱导型启动子控制下的大鼠抗酶cDNA的pMAMneoZ 1转染ODC过量产生细胞。在转染的细胞中，地塞米松的加入引起的表观分子量为27 kDa的抗酶的量的增加，ODC的量的减少，多胺转运活性的降低，和生长抑制或细胞死亡的恢复。结果表明，抗酶不仅可以调节ODC的数量，而且可以调节多胺转运的活性。
Exposure of ornithine decarboxylase (ODC; L-ornithine carboxy-lyase, EC 4.1.1.17)-overproducing mouse FM3A cells to micromolar levels of spermine or spermidine caused abnormal accumulation and toxicity of polyamines. This was apparently due to the inefficiency of negative feedback control of polyamine transport by polyamines in ODC-overproducing cells. Since antizyme is the only protein thus far recognized that can interact with ODC, depletion of free antizyme was regarded as the reason for the abnormal accumulation of polyamines. Accordingly, ODC-overproducing cells were transfected with pMAMneoZ1 possessing rat antizyme cDNA under the control of a glucocorticoid-inducible promoter. In the transfected cells, the addition of dexamethasone caused an increase in the amount of antizyme with an apparent molecular mass of 27 kDa, a decrease in the amount of ODC, a decrease in the polyamine transport activity, and the recovery of growth inhibition or cell death. The results indicate that antizyme can regulate not only the amount of ODC but also the activity of polyamine transport.