Superfund Research Program
Monitoring Endoplasmic Reticulum Stress Caused by Chronic Exposure to Chemicals
Project Leader: Fawaz G. Haj
Grant Number: P42ES004699
Funding Period: 2017-2022
Project researchers used HEK293 and HUVEC cell lines to screen the ability of 176 Superfund chemicals at 10 micromolar to create cellular stress. The assay was able to identify known cytotoxic phenolic compounds, but also the antibacterial triclosan and insecticide bathroid. The researchers are now using primary hepatocytes to investigate the effects of these chemicals on cellular inflammation, which can contribute to several diseases, including obesity, arthritis, and Alzheimer’s disease (Bailey et al, 2019; Lang et al, 2019; McReynolds et al, 2019). In animal models (male mice, rats, and dogs), exposure to xenobiotics such as dimethylsulfoxide, or the insecticides permethrin and diisopropylfluorophosphate, yields local inflammatory response and dysregulates the normal balance of endogenous lipid mediators, in part through the increase expression of soluble epoxide hydrolase (sEH), which leads to endoplasmic reticulum (ER) stress and organ damage (Deaol et al, 2019; Joshi et al 2019; Yang et al, 2019). This was associated with cancer, chronic inflammation, diabetes, hypertension, liver injury, and neurologic disorders (Gartung et al, 2019; Hrdilicka et al, 2019; Klocke et al, 2019; Luo et al, 2019; McReynolds et al, 2019; Ma et al, 2019; Minaz et al, 2019; Otoki et al, 2019; Pardeshi et al, 2109; Shen et al, 2019; Wang et al , 2019; Zhang et al, 2019) - diseases known to be influenced by environmental exposure and present in the principal community supported by the UC Davis Superfund Research Center, highlighting the relevance to report finding to the stakeholder(s).