Fig. 5.

Summary of the effects of RUPP treatment and HO-1 induction on the cell survival signaling pathways in the placenta. In response to RUPP treatment, signaling mediators of cell injury (i.e., STAT1 and JNK) are activated in the placenta, indicating a proinjury state. Induction of HO-1, however, attenuates the activation of these pathways, and increases the activation of prosurvival signaling, such as ERK and STAT3. In consequence, the induction of caspase-3 and depletion of ATP seen in the RUPP placenta are significantly reduced, shifting the balance of cell signaling from a proinjury state to a prosurvival state.