Plasmodium falciparum:: The fungal metabolite gliotoxin inhibits proteasome proteolytic activity and exerts a plasmodicidal effect on Plasmodium falciparum
Plasmodium falciparum:: The fungal metabolite gliotoxin inhibits proteasome proteolytic activity and exerts a plasmodicidal effect on Plasmodium falciparum
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DOI：
10.1016/j.exppara.2005.11.012
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发表时间：
2006-03-01
影响因子：
2.1
通讯作者：
Sato, K
中科院分区：
文献类型：
--
作者：
Hatabu, T;Hagiwara, M;Sato, K
对真菌代谢物胶质毒素（GTX）的体外抗疟活性进行了评价，并对其作用机制进行了研究。GTX对恶性疟原虫氯喹耐药菌株K-1和氯喹敏感菌株FCR-3均有杀疟原虫活性。GTX对正常肝细胞系（Chang肝细胞）的细胞毒性显著降低。GTX处理对寄生红细胞和正常红细胞胞内还原性谷胱甘肽水平无影响。然而。GTX以时间依赖性的方式降低寄生虫蛋白酶体的凝乳胰蛋白酶样活性。本研究结果表明，GTX具有杀疟原虫活性，这种作用是由于抑制寄生虫蛋白酶体的活性，提示GTX可能是一种有用的抗疟疾药物。(c) 2005爱思唯尔公司版权所有。
The in vitro antimalarial activity of the fungal metabolite gliotoxin (GTX) was evaluated, and its mechanism of action was studied. GTX showed plasmodicidal activity against both Plasniodium falciparum chloroquine-resistant strain K-1 and chloroquine-susceptible strain FCR-3. GTX cytotoxicity was significantly lower against a normal liver cell line (Chang Liver cells). The intracellular reduced glutathione level of parasitized and of normal red blood cells was not affected by GTX treatment. However. GTX decreased the chymotrypsin-like activity of parasite proteasomes in a time-dependent manner. The results of this study indicate that GTX possesses plasmodicidal activity and that this effect is due to inhibition of parasite proteasome activity, suggesting that GTX may constitute a useful antimalarial therapy. (c) 2005 Elsevier Inc. All rights reserved.