PCB 126 toxicity is modulated by cross-talk between caveolae and Nrf2 signaling.

PCB 126 toxicity is modulated by cross-talk between caveolae and Nrf2 signaling. Toxicol Appl Pharmacol. 2014 Apr 4; Authors: Petriello MC, Han SG, Newsome BJ, Hennig B Abstract Environmental toxicants such as polychlorinated biphenyls (PCBs) have been implicated in the promotion of multiple inflammatory disorders including cardiovascular disease, but information regarding mechanisms of toxicity and cross-talk between relevant cell signaling pathways is lacking. To examine the hypothesis that cross-talk between membrane domains called caveolae and nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathways alter PCB-induced inflammation, caveolin-1 was silenced in vascular endothelial cells, resulting in a decreased PCB-induced inflammatory response. Cav-1 silencing (siRNA treatment) also increased levels of Nrf2-ARE transcriptional binding, resulting in higher mRNA levels of the antioxidant genes glutathione s-transferase and NADPH dehydrogenase quinone-1 in both vehicle and PCB-treated systems. Along with this upregulated antioxidant response, Cav-1 siRNA treated cells exhibited decreased mRNA levels of the Nrf2 inhibitory protein Keap1 in both vehicle and PCB-treated samples. Silencing Cav-1 also decreased protein levels of Nrf2 inhibitory proteins Keap1 and Fyn kinase, especially in PCB-treated cells. Further, endothelial cells from wildtype and Cav-1-/- mice were isolated and treated with PCB to better elucidate the role of func...
Source: Toxicology and Applied Pharmacology - Category: Toxicology Authors: Tags: Toxicol Appl Pharmacol Source Type: research