Spermidine is essential for normal proliferation of trypanosomatid protozoa

Spermidine is essential for normal proliferation of trypanosomatid protozoa
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DOI:
10.1016/s0014-5793(01)03091-5
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发表时间:
2001-11-23
期刊:
影响因子:
3.5
通讯作者:
Algranati, ID
Algranati, ID
中科院分区:
生物学3区
文献类型:
--
作者:
González, NS;Huber, A;Algranati, ID

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含有代谢不稳定的鸟氨酸脱羧酶(ODC)的锥虫寄生虫对高水平的α-二氟甲基鸟氨酸(DFMO)具有天然抗性,因为这种ODC抑制剂虽然引起细胞内腐胺的急剧减少,但仅引起亚精胺内源性库的适度减少。在这项研究中,我们使用了DFMO与环己胺(CHA;双环己基硫酸铵),亚精胺合酶的抑制剂的组合,达到更完全的亚精胺耗尽。在这些条件下,我们观察到的增殖逮捕不仅在锥虫与稳定的ODC,但也在寄生虫与高周转率的酶。在所有的情况下,增殖的重新启动后,才发生的外源亚精胺,腐胺和精胺都不能诱导同样的效果。(C)2001年欧洲生物化学学会联合会。由Elsevier Science B. V.出版,版权所有。
Trypanosomatid parasites containing a metabolically unstable ornithine decarboxylase (ODC) are naturally resistant to high levels of oc-difluoromethylornithine (DFMO) because this ODC inhibitor, though causing a drastic reduction of intracellular putrescine, elicits only a moderate decrease of the spermidine endogenous pool. In this study we have used a combination of DFMO with cyclohexylamine (CHA; bis-cyclohexylammonium sulfate), an inhibitor of spermidine synthase, to reach a more complete depletion of spermidine. Under these conditions we have observed the arrest of proliferation not only in trypanosomatids with stable ODC but also in parasites with an enzyme of high turnover rate. In all cases the reinitiation of proliferation occurred only after the addition of exogenous spermidine, and neither putrescine nor spermine were able to induce the same effect. (C) 2001 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.