The goal of this proposed research is to determine whether 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD)-induced oxidative stress leads to the development of insulin resistance. The mouse pre-adipocyte cell line (3T3-L1) will be used as an in vitro model system to study TCDD-induction of insulin resistance. The goal of this research will be pursued through studies in two specific aims.
The first aim i s to determine whether TCDD exposure leads to insulin resistance in 3T3-L1 cells by inducing oxidative stress. The effects of TCDD on activity and mRNA levels of the antioxidant glutathione peroxidase (GSH-PX), catalase, and superoxide dismutase will be evaluated. Additionally, evidence of oxidative damage will be assessed by measuring lipid peroxidation and DNA strand breaks.
The second aim i s designed to determine whether TCDD-induced insulin resistance in 3T3-L1 cells can be blocked by overexpression of GSH-Px.
| Kern, Philip A; Fishman, Renata B; Song, Wei et al. (2002) The effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on oxidative enzymes in adipocytes and liver. Toxicology 171:117-25 |
