Topoisomerase II inhibitors induce cleavage of nuclear and 35-kb plastid DNAs in the malarial parasite Plasmodium falciparum.
Topoisomerase II inhibitors induce cleavage of nuclear and 35-kb plastid DNAs in the malarial parasite Plasmodium falciparum.
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拓扑异构酶 II 抑制剂可诱导恶性疟原虫中核 DNA 和 35 kb 质体 DNA 的裂解。
DOI：
10.1089/dna.1997.16.1483
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发表时间：
1997
期刊：
影响因子：
--
通讯作者：
Rowe,TC
中科院分区：
文献类型：
--
作者：
Weissig,V;Vetro-Widenhouse,TS;Rowe,TC
使用拓扑异构酶 II 特异性抑制剂 VP-16 和环丙沙星来研究与疟原虫恶性疟原虫的核 DNA 和 35 kb 质体 DNA 相关的拓扑异构酶 II 活性的存在。真核拓扑异构酶 II 抑制剂 VP-16 诱导细胞核 DNA 和 35 kb 寄生虫 DNA 的裂解。相比之下，环丙沙星（一种已知作用于细菌 II 型拓扑异构酶 DNA 旋转酶的氟喹诺酮药物）仅诱导疟原虫 35-kb DNA 的裂解。药物诱导的切割导致被切割的核和 35-kb DNA 的 5'- 末端得到保护，而不是 3'- 末端被核酸外切酶消化，这表明断裂 DNA 的 5'- 末端是蛋白连接的，这一特性让人想起拓扑异构酶 II 介导的 DNA 切割。此外，VP-16 和环丙沙星诱导的 DNA 裂解是热可逆的。这是第一个证据表明P.恶性疟原虫含有两种不同的拓扑异构酶 II 活性，它们是化疗药物的分子靶标。
The topoisomerase II-specific inhibitors VP-16 and ciprofloxacin were used to investigate the presence of topoisomerase II activities associated with nuclear and 35-kb plastid DNAs of the malarial parasitePlasmodium falciparum. The eukaryotic topoisomerase II inhibitor VP-16 induced cleavage of both nuclear and 35-kb parasite DNAs. In contrast, ciprofloxacin, a fluoroquinolone drug known to act on the bacterial type II topoisomerase DNA gyrase, only induced cleavage of thePlasmodial35-kb DNA. Drug-induced cleavage resulted in the protection of the 5′- but not 3′- ends of the cleaved nuclear and 35-kb DNAs from exonuclease digestion, suggesting that the 5′-ends of the broken DNA were protein-linked, a property reminiscent of DNA cleavage mediated by topoisomerase II enzymes. Furthermore, DNA cleavage induced by both VP-16 and ciprofloxacin was heat-reversible. This is the first evidence thatP. falciparumcontains two distinct topoisomerase II activities that are molecular targets for chemotherapeutic agents.