Effects of PCB-126 on aryl hydrocarbon receptor, ubiquitin and p53 expression levels in Sparus aurata.

Abstract

The aim of the present study is to determine if Ahr ligands as PCB-126, a dioxin-like, might contribute to inhibition of the tumor suppressor p53 by promoting its degradation through proteasome-ubiquitin system (UPS). The findings show, in the presence of PCB-126, a significant increase of p53 immunoreactivity in fish compared to the control. Subsequently, there is a decrease of p53 immunoreactivity at 24h which is maintained even at 72h. At the same time there is a slight decrease of ubiquitin immunoreactivity to 12h compared to the control and a marked decrease to 24 and 72h. The induction of ubiquitin expression is resulted very marked in the control and preserved at 12h. It's very important to underline as in our study we demonstrate a marked decrease of ubiquitin and p53 immunoreactivity at 24h and 72h. AHR activation, by ligands as PCB-126, increases p53 ubiquitation inhibiting its expression, in addition it decreases the free ubiquitin promoting disruption of Ub homeostasis; this is the first report that establishes a relationship between AhR, increases p53 ubiquitation, and reduction of free ubiquitin. Our result emphasize the need to deeply the role of this receptor in UPS regulation as potential therapeutic target for cancer treatment.