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猫抑胃肽,一种内源性嗜铬粒蛋白 A 衍生肽,可抑制恶性疟原虫的体外生长。

Catestatin, an endogenous chromogranin A-derived peptide, inhibits in vitro growth of Plasmodium falciparum.

机构信息

Institut de Parasitologie et de Pathologie Tropicale, Université de Strasbourg, France.

出版信息

Cell Mol Life Sci. 2010 Mar;67(6):1005-15. doi: 10.1007/s00018-009-0235-8. Epub 2009 Dec 31.

Abstract

Catestatin, an endogenous peptide derived from bovine chromogranin A, and its active domain cateslytin display powerful antimicrobial activities. We have tested the activities of catestatin and other related peptides on the growth of Plasmodium falciparum in vitro. Catestatin inhibits growth of the chloroquine-sensitive strain of P. falciparum 3D7, exhibiting 88% inhibition at 20 microM. A similar partial inhibition of parasite growth was observed for the chloroquine-resistant strain, 7G8 (64%,) and the multidrug-resistant strain, W2 (62%). In the presence of parasite-specific lactate dehydrogenase, a specific protein-protein interaction between catestatin and plasmepsin II precursor was demonstrated. In addition, catestatin partially inhibited the parasite-specific proteases plasmepsin in vitro. A specific interaction between catestatin and plasmepsins II and IV from P. falciparum and plasmepsin IV from the three remaining species of Plasmodium known to infect man was observed, suggesting a catestatin-induced reduction in availability of nutrients for protein synthesis in the parasite.

摘要

猫抑胃肽,一种源于牛嗜铬粒蛋白 A 的内源性肽,以及其活性结构域猫抑胃肽,具有强大的抗菌活性。我们已经测试了猫抑胃肽和其他相关肽对体外疟原虫生长的活性。猫抑胃肽抑制氯喹敏感株 3D7 的生长,在 20μM 时表现出 88%的抑制率。对氯喹耐药株 7G8(64%)和多药耐药株 W2(62%)也观察到类似的寄生虫生长部分抑制。在寄生虫特异性乳酸脱氢酶存在的情况下,证明了猫抑胃肽与原裂殖体蛋白酶 II 前体之间的特异性蛋白-蛋白相互作用。此外,猫抑胃肽在体外部分抑制了寄生虫特异性蛋白酶裂殖体蛋白酶。观察到猫抑胃肽与疟原虫的裂殖体蛋白酶 II 和 IV 以及已知感染人类的另外三种疟原虫的裂殖体蛋白酶 IV 之间的特异性相互作用,这表明猫抑胃肽诱导减少了寄生虫蛋白质合成所需的营养物质的可利用性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c98/11115691/21129359537a/18_2009_235_Fig1_HTML.jpg

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