Department of Biochemistry and Molecular Biology IV, Universidad Complutense de Madrid, Facultad de Veterinaria, Ciudad Universitaria, 28040 Madrid, Spain.
Acta Trop. 2010 May;114(2):109-15. doi: 10.1016/j.actatropica.2010.01.013. Epub 2010 Feb 6.
Resistance to chloroquine (CQ) in Plasmodium falciparum has a major impact on malaria control worldwide. To gain insight into early parasite stress response, mRNA expression profiles were determined for a set of 10 antioxidant defence genes in synchronized CQ-sensitive (3D7) and CQ-resistant (Dd2) clones under transient IC50 CQ-exposure (Dd2, 200 nM; 3D7, 14 nM). Upon 2-h CQ challenge, the mRNA upregulation detected was greater in 3D7 (six genes overexpressed at 1/3 of the intraerythrocytic cycle) than in Dd2 clone (three genes responding), providing evidence of an early transcriptional response to CQ-induced oxidative stress which might underlie some of the parasite's metabolic adaptation to the drug.
疟原虫对氯喹(CQ)的耐药性对全球疟疾控制产生了重大影响。为了深入了解早期寄生虫应激反应,在短暂的 IC50 CQ 暴露下(Dd2,200 nM;3D7,14 nM),对一组 10 种抗氧化防御基因的 mRNA 表达谱进行了测定,用于同步的 CQ 敏感(3D7)和 CQ 耐药(Dd2)克隆。在 2 小时的 CQ 挑战后,3D7 中检测到的 mRNA 上调幅度大于 Dd2 克隆(六个基因在红细胞内周期的 1/3 处过度表达),这表明对 CQ 诱导的氧化应激存在早期转录反应,这可能是寄生虫对药物代谢适应的部分原因。