Stress Response, p97, and Nrf2 in Arsenic-Mediated Toxicity

With pilot project funds we were able to collect sufficient preliminary data to successfully compete for an R01 (ES023758). The preliminary data collected were able to show p97 is directly affected by arsenic. In particular, the ATPase rate of p97 is increased in the presence of arsenic. This was meaningful because a series of genetic lesions has been shown to cause an increase in p97 ATPase activity, which leads to a compromise of autophagy. We also observed this compromise in the presence of arsenic, offering a potential link between arsenic exposure, protein quality control, and Nrf2 signaling. In addition, we showed a direct link between p97 and Nrf2. All of these data have added a potential critical connection between arsenic exposure and cellular transformation.  With this support we were able to collect preliminary data and successfully competed for a Ro1 (ES023758) to address arsenic induce p97 due to stress response.  Additional we are preparing manuscripts for publication.