Effect of antisense-SGTPs on the glucose uptake of the blood fluke Schistosoma mansoni: observations in adult worms and schistosomula.
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%.
Wongwit
Waranya
W
Department of Social and Environmental Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
Rivera
Ezequiel
E
Tao
Liang-Feng
LF
D000818:Animals; D001483:Base Sequence; D001786:Blood Glucose / Q000096:biosynthesis*; D018797:Cell Cycle Proteins / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D018390:Gene Targeting; D008297:Male; D008969:Molecular Sequence Data; D009004:Monosaccharide Transport Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D016376:Oligonucleotides, Antisense / Q000008:administration & dosage / Q000378:metabolism*; D012550:Schistosoma mansoni / Q000235:genetics / Q000378:metabolism*
D001786:Blood Glucose; D018797:Cell Cycle Proteins; D009004:Monosaccharide Transport Proteins; D016376:Oligonucleotides, Antisense; C490164:SUGT1 protein, human