Figure 7. Cry5B PFT activate the hypoxia pathway and hypoxia confers protection against PFTs.

(A) Quantitative real-time PCR analysis of nhr-57 expression in glp-4(bn2) animals upon treatment on Cry5B for 1, 2, 4 and 8 hours relative to expression levels in no-toxin treatment animals. Data are averaged from three independent experiments. Error bars represent standard error of the mean, * represents P value<0.05 and *** P value<0.001. (B) Resistance to Cry5B PFT was compared among wild-type N2 worms in normoxia (top two rows) and in hypoxia (2% O₂) (rows 3 and 4) and among hif-1(ia04) mutant animals in normoxia (rows 5 and 6) and in hypoxia (bottom two rows). Wild-type worms co-treated with hypoxia and Cry5B are significantly healthier (larger, darker color, more embryos, more motile) than worms treated with Cry5B under normoxia. In contrast, hif-1(ia04) mutant animals on Cry5B PFT look similarly sick either in the normoxic or in the hypoxic environment. Scale bar is 0.2 mm. (C) Schematic illustrating our results and relationship between the HIF-1 pathway and PFT INCED. In response to PFT, the hypoxia response is activated by suppression of EGL-9, either by low oxygen and/or other means. HIF-1 activates expression of target genes that protect against PFT intoxication, such as nhr-57. Activation of HIF-1 is also able to activate the XBP-1 arm of the UPR defense pathway.