93.3 Tuesday, Jan. 6 14:00 Heat and oxidative stress synergize to reduce survival and inhibit expression of stress response genes in the nematode Caenorhabditis elegans CROMBIE, TA*; JULIAN, D; Univ. of Florida, Gainesville; Univ. of Florida, Gainesville firstname.lastname@example.org
Maintenance of homeostasis may be especially challenging in habitats characterized by large variations in external environmental parameters, such as fluctuations in temperature and redox potential. Deviations in such parameters can temporarily disrupt homeostasis or "stress" an organism, potentially leading to reduced energy, fitness, and survival, depending on the intensity and duration of the stress. We recently showed that heat and oxidative stress interact synergistically to reduce survival in the nematode C. elegans. Whereas animals grown at 20 °C and then exposed to heat stress (35 °C for 4 h) had 0 % mortality, and animals exposed to oxidative stress via the redox cycling compound juglone (100 μM for 4 h) had 30 % mortality, animals exposed to the combination of heat and oxidative stress (35 °C and 100 μM juglone for 4 h) had 91 % mortality, which is 61 % greater than expected assuming an additive model. Here we tested whether impaired expression of stress response genes plays a role in the observed synergistic interaction between heat and oxidative stress. In the case of juglone-induced oxidative stress, glutathione S-transferases (gsts) are expressed to detoxify juglone. Using a reporter strain containing GFP fused to the promoter fragment upstream of gst-4, we found that induction of gst-4 by juglone was inhibited at temperatures greater than 30 °C. We validated this result with qPCR, which showed an 18.7-fold increase in expression of gst-4 in response to 20 μM juglone at 20 °C, but only a 5.9-fold increase in gst-4 expression at 33 °C. We found similar, heat-dependent inhibition for other isoforms of gst. These findings suggest that a heat-dependent inhibition of gst induction is at least one mechanism by which heat and oxidative stress synergize to reduce nematode survival.