Department of Biology, Brandon University, Brandon, Manitoba, Canada.
Exp Parasitol. 2011 Oct;129(2):137-44. doi: 10.1016/j.exppara.2011.06.018. Epub 2011 Jul 13.
Some ABC transporters play a significant role in human health and illness because they confer multidrug resistance (MDR) through their overexpression. Compounds that inhibit the drug efflux mechanism can improve efficacy or reverse resistance. Of the eight described ABC transporter subfamilies, those proteins conferring MDR in humans are in subfamilies A, B, C, and G. In nematodes, transporters in subfamilies B and C are suggested to confer resistance to ivermectin. The Brugia malayi ABC transporter superfamily was examined to assess their potential to influence sensitivity to moxidectin. There was an increase in expression of ABC transporters in subfamilies A, B, C, and G following treatment. Co-administration of moxidectin with inhibitors of ABC transporter function did not enhance sensitivity to moxidectin in males; however, sensitivity was significantly enhanced in females and microfilariae. The work suggests that ABC transporters influence sensitivity to moxidectin and have a potential role in drug resistance.
一些 ABC 转运蛋白在人类健康和疾病中发挥着重要作用，因为它们通过过度表达赋予了多药耐药性（MDR）。抑制药物外排机制的化合物可以提高疗效或逆转耐药性。在描述的八个 ABC 转运蛋白亚家族中，那些在人类中赋予 MDR 的蛋白质存在于 A、B、C 和 G 亚家族中。在线虫中，B 和 C 亚家族的转运蛋白被认为对抗虫菌素具有抗性。检查了班氏丝虫 ABC 转运蛋白超家族，以评估它们对莫昔克丁敏感性的潜在影响。在治疗后，亚家族 A、B、C 和 G 中的 ABC 转运蛋白表达增加。莫昔克丁与 ABC 转运蛋白功能抑制剂联合使用并未增强雄性对莫昔克丁的敏感性；然而，在雌性和微丝蚴中，敏感性显著增强。这项工作表明，ABC 转运蛋白影响莫昔克丁的敏感性，并在耐药性中具有潜在作用。
