抗叶酸药物对弓形虫二氢叶酸还原酶（DHFR）酶活性及表达的影响
Changes in enzyme activity and expression of DHFR of Toxoplasma gondii by antifolates.
作者信息
Baek E J, Nam H W
机构信息
Department of Parasitology, College of Medicine, Catholic University of Korea, Seoul, Korea.
出版信息
Korean J Parasitol. 1998 Sep;36(3):191-8. doi: 10.3347/kjp.1998.36.3.191.
The responses to antifolates of Toxoplasma gondii were investigated by measuring the dihydrofolate reductase (DHFR) activity, quantity of DHFR mRNA, and single-strand conformational polymorphism (SSCP) pattern. Pyrimethamine (PYM) and methotrexate (MTX) were tested as antifolates. When T. gondii was treated with PYM, the viability was decreased by the increasing concentration of PYM, DHFR activity tended to increase as the passage proceeded, and the quantity of mRNA expressed was also increased according to passages. The viability of T. gondii was decreased by the increasing concentration of MTX, but it was maintained over 40% up to 100 microM MTX. DHFR activity was 77.4% in the 1st passage (1 microM). 82.2% in the 4th passage (10 microM), and 141.3% in the 7th passage (100 microM). But no changes were detected in SSCP pattern of T. gondii exposed to PYM and MTX, both. These results suggested that the response of T. gondii to PYM was regulated by transcriptional level and that, in MTX, the viability of T. gondii was derived from increasing DHFR activity.
通过测量二氢叶酸还原酶（DHFR）活性、DHFR mRNA数量和单链构象多态性（SSCP）模式，研究了弓形虫对抗叶酸药物的反应。以乙胺嘧啶（PYM）和甲氨蝶呤（MTX）作为抗叶酸药物进行测试。当用PYM处理弓形虫时，随着PYM浓度的增加，其活力降低，随着传代进行，DHFR活性趋于增加，并且表达的mRNA数量也随传代增加。随着MTX浓度的增加，弓形虫的活力降低，但在高达100 microM的MTX浓度下仍保持在40%以上。在第1代（1 microM）时DHFR活性为77.4%，第4代（10 microM）时为82.2%，第7代（100 microM）时为141.3%。但暴露于PYM和MTX的弓形虫的SSCP模式均未检测到变化。这些结果表明，弓形虫对PYM的反应受转录水平调节，而在MTX作用下，弓形虫的活力源自DHFR活性的增加。
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