Research Paper Volume 5, Issue 10 pp 759—769

A DNA synthesis inhibitor is protective against proteotoxic stressors via modulation of fertility pathways in Caenorhabditis elegans

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Figure 1. FUdR is protective under various conditions of proteotoxic stress. A, Temperature-sensitive strain, HE250 [unc-52(e669su250)II], which expresses the misfolded basement membrane protein, perlecan, was scored for paralysis 24 hours after shifting to the restrictive temperature of 25°C (day 1 of adulthood) in the absence or presence of increasing concentrations of FUdR. FUdR-treatment rescues paralysis at all concentrations. (*=p<0.05, **=p<0.01, Student's t-test) B, Temperature-sensitive strain, CL4176 [smg-1 (cc546ts); dvIs27(myo-3::Aβ3−42 let 39UTR(pAF29))], which expresses amyloid-β3-42 peptide, was scored for paralysis on day 5 of adulthood in the absence or presence of increasing concentrations of FUdR. FUdR-treatment rescues paralysis at all concentrations. (**=p<0.01, Student's t-test) C, Temperature-sensitive strain, AM141 [rmIs133(P(unc-54) Q40::YFP)], which expresses a polyglutamine stretch of 40 repeats, was transiently exposed to FUdR during spermatogenesis and scored for motility on day 5 of adulthood. FUdR-treatment (100 μg/ml) significantly improves motility as measured by number of body bends. (**=p<0.001, Student's t-test) D, FUdR-treatment (100 μg/ml) significantly extends the survival of wild-type N2 animals at 35°C. (p=<0.001, Log rank Mantel-Cox).