Independent roles of eIF5A and polyarnines in cell proliferation
Independent roles of eIF5A and polyarnines in cell proliferation
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DOI：
10.1042/bj20041477
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发表时间：
2005-02-01
影响因子：
4.1
通讯作者：
Igarashi, K
中科院分区：
文献类型：
--
作者：
Nishimura, K;Murozumi, K;Igarashi, K
为探讨活化的真核翻译起始因子5A(EIF5A)和多胺在细胞增殖中的作用，用脱氧亚硫氨酸合成酶抑制剂GC(7)(N-1-鸟氨基-1，7-二氨基庚烷)或鸟氨酸脱羧酶抑制剂DFMO(α-二氟甲基亚胺)或DFMO+精胺合成酶抑制剂APCHA[N‘-(3-氨丙基)环己胺]处理小鼠乳腺癌FM3A细胞。经GC(7)处理后，活性eIF5/水平下降。这种延迟反映了eIF5A在这些细胞中过量存在且非常稳定的事实。DFMO或DFMO+APCHA处理第1天抑制细胞生长。DFMO显著降低腐胺和亚精胺水平，当亚精胺水平降至8nmol/mg蛋白以下时，活性eIF5A的形成开始减少。DFMO和APCHA联合应用可显著降低腐胺和精胺水平，显著降低精胺水平，但直到第3天精胺水平降至7nmol/mg蛋白质时才对活性eIF5A水平产生影响。结果表明，活性eIF5A或多胺的减少抑制了细胞的生长，表明elF5A和多胺独立地参与细胞的生长。
To exam ne the roles of active hypusinated eIF5A (eukaryotic translation initiation factor 5A) and polyamines in cell proliferation, mouse mammary carcinoma FM3A cells were treated with an inhibitor of deoxyhypusine synthase, GC(7) (N-1-guanyl-1, 7-diaminoheptane), or with an inhibitor of ornithine decarboxylase, DFMO (alpha-difluoromethylomithine), or with DFMO plus an inhibitor of spermine synthase, APCHA [N'-(3-aminopropyl)cyclohex ylamine]. Treatment with GC(7) decreased the level of active eIF5/. on day I without affecting cellular polyamine content, and inhibition of cell growth occurred from day 2. This delay reflects the fact that eIF5A was present in excess and was very stable in these cells. Treatment with DFMO or with DFMO plus APCHA inhibited cell growth on day 1. DFMO considerably decreased the levels of putrescine and spermidine, and the formation of active eIF5A began to decrease when the level of spermidine fell below 8 nmol/mg of protein after 12 h of incubation with DFMO. The combination of DFMO and APCHA markedly decreased the levels of putrescine and spermine and significantly decreased the level of spermidine, but did not affect the level of active eIF5A until day 3 when spermidine level decreased to 7 nmol/mg of protein. The results show that a decrease in either active eIF5A or polyamines inhibits cell growth, indicating that elF5A and polyamines are independently involved in cell growth.