Serra E C, Lardans V, Dissous C
Unite 167 INSERM, Institut Pasteur, Lille, France.
Mol Biochem Parasitol. 1999 Jun 25;101(1-2):33-41. doi: 10.1016/s0166-6851(99)00046-8.
Cyclosporin A (CsA) has been found to exert potent anti-parasite activity against a wide range of protozoan and helminth parasites. In schistosomes, evidence has been accumulated to propose that the drug damages parasites by mechanisms independent of its immunosuppressive properties. Moreover, the absence of correlation between anti-schistosomal properties and inhibition of peptidyl-prolyl cis-trans isomerase activity of cyclophilins (CsA receptors) for various drug analogs, argued against a direct implication of cyclophilins in the lethal effect of CsA. We describe, in S. mansoni, the existence of NF-AT-like transcription factors, a protein family already characterized by its sensitivity to CsA. The observation that CsA treatment of S. mansoni larvae inhibited the expression of the Sm28GST protein and the characterization of a functional NF-AT-like site in the gene encoding this protein, provide new insights in the understanding of the antischistosomal effect of CsA. Our results also support the hypothesis that the regulatory function of NF-AT-like proteins might be responsible for parasite development and survival in the host and open new perspectives in studies of helminth biology.
已发现环孢素A（CsA）对多种原生动物和蠕虫寄生虫具有强大的抗寄生虫活性。在血吸虫中，已有证据表明该药物通过与其免疫抑制特性无关的机制损害寄生虫。此外，各种药物类似物的抗血吸虫特性与亲环蛋白（CsA受体）的肽基脯氨酰顺反异构酶活性抑制之间缺乏相关性，这表明亲环蛋白与CsA的致死作用没有直接关联。我们在曼氏血吸虫中描述了类NF-AT转录因子的存在，这是一个已因其对CsA敏感而被鉴定的蛋白质家族。CsA处理曼氏血吸虫幼虫会抑制Sm28GST蛋白的表达，以及在编码该蛋白的基因中鉴定出一个功能性类NF-AT位点，这些发现为理解CsA的抗血吸虫作用提供了新的见解。我们的结果还支持这样的假设，即类NF-AT蛋白的调节功能可能负责寄生虫在宿主体内的发育和存活，并为蠕虫生物学研究开辟了新的前景。
