EFFECT OF POLYAMINE DEPLETION ON MACROMOLECULAR-SYNTHESIS OF THE MALARIAL PARASITE, PLASMODIUM-FALCIPARUM, CULTURED IN HUMAN-ERYTHROCYTES

EFFECT OF POLYAMINE DEPLETION ON MACROMOLECULAR-SYNTHESIS OF THE MALARIAL PARASITE, PLASMODIUM-FALCIPARUM, CULTURED IN HUMAN-ERYTHROCYTES
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DOI:
10.1042/bj2420221
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发表时间:
1987-02-15
影响因子:
4.1
通讯作者:
BACHRACH, U
BACHRACH, U
中科院分区:
生物学3区
文献类型:
--
作者:
ASSARAF, YG;ABUELHEIGA, L;BACHRACH, U

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DL-α-二氟甲基鸟氨酸(DFMO),一种不可逆的鸟氨酸脱羧酶抑制剂,防止腐胺和亚精胺,但不是精胺,在感染恶性疟原虫的人红细胞的增加。此外,腐胺这些多胺耗尽文化恢复正常浓度的亚精胺,而腐胺甚至超过了控制文化。DFMO还抑制放射性氨基酸掺入寄生红细胞的蛋白质中。聚丙烯酰胺凝胶电泳显示,DFMO完全阻断了某些蛋白质的合成,但其他蛋白质的合成不受影响。DFMO还引起RNA合成的部分抑制,DNA合成被完全阻断在多胺耗尽寄生红细胞。有人提出,腐胺和/或亚精胺是在寄生红细胞中合成某些蛋白质所必需的,并且这些蛋白质中至少有一种与疟疾寄生虫的DNA合成有关。看来多胺调节恶性疟原虫的生殖过程。
DL-.alpha.-Difluoromethylornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase, prevented the increases in putrescine and spermidine, but not in spermine, in human erythrocytes infected with the malarial parasite Plasmodium falciparum. The addition of putrescine to these polyamine-depleted cultures restored the normal concentrations of spermidine, whereas that of putrescine even exceeded that of the control cultures. DFMO also inhibited the incorporation of radioactive amino acids into the proteins of parasitized erythrocytes. Electrophoresis on polyacrylamide gels revealed that the synthesis of some proteins was completely blocked by DFMO, but the synthesis of others was not affected. DFMO also caused a partial inhibition of RNA synthesis, and DNA synthesis was completely blocked in polyamine-depleted parasitized erythrocytes. It has been suggested that putrescine and/or spermidine are required for the synthesis of certain proteins in parasitized erythrocytes and that at least one of those proteins is related to the synthesis of DNA of the malarial parasite. It appears that polyamines regulate the schizogony process of P. falciparum.