Wongwit Waranya, Rivera Ezequiel, Tao Liang-Feng
Department of Social and Environmental Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
Southeast Asian J Trop Med Public Health. 2005 Jan;36(1):83-8.
AS-ODNs, complementary to Schistosoma mansoni glucose transporter proteins (SGTP1 and SGTP4), were chosen as potential therapeutic agents for schistosomiasis. AS-SGTP1 oligos lowered the glucose uptake of adult worms both in vitro and ex vivo. The most effective AS-ODN was that of 21 nucleotides complementary to the SGTP1 nucleotide sequence, including the initiation region of mRNA translation. This oligo was found to decrease glucose uptake in vitro by as much as 50% and at a concentration of 4.0 mg/ml, it killed all male worms within 24 hours. A significant decrease, up to 34%, in glucose uptake was also noted when 100 mg/kg x2 (with a 2 hours interval) of AS-ODN was administered ex vivo. Two out of six anti-SGTP4 oligos also decreased the glucose uptake of adult worms in vitro by 25-44%. Added to the culture of schistosomula, two AS-SGTP4 oligos were found to decrease glucose uptake by 20-43%.
与曼氏血吸虫葡萄糖转运蛋白(SGTP1和SGTP4)互补的反义寡核苷酸(AS-ODNs)被选为血吸虫病的潜在治疗药物。AS-SGTP1寡核苷酸在体外和离体条件下均降低了成虫的葡萄糖摄取。最有效的AS-ODN是与SGTP1核苷酸序列互补的21个核苷酸的寡核苷酸,包括mRNA翻译的起始区域。该寡核苷酸在体外可使葡萄糖摄取降低多达50%,在浓度为4.0mg/ml时,在24小时内杀死了所有雄虫。当以100mg/kg×2(间隔2小时)的剂量离体给予AS-ODN时,葡萄糖摄取也显著降低,高达34%。六种抗SGTP4寡核苷酸中的两种在体外也使成虫的葡萄糖摄取降低了25%-44%。添加到童虫培养物中后,发现两种AS-SGTP4寡核苷酸可使葡萄糖摄取降低20%-43%。