Co-regulators of autophagy and the cell cycle in HFD − As treated mice

Abstract

In stressful conditions, cells can have either temporary or irreversible cell cycle arrest. This ability helps regulate proliferation and differentiation and prevent the spread of cell populations that can be harmful. Similar to cell cycle arrest, autophagy is induced or inhibited as a function of different stressful conditions and plays a key role in protecting the cell. In our previous study, it was shown that exposure to arsenic (As) and high-fat diet (HFD) resulted in the upregulation of autophagy. In this study, we used gene expression profiling of co-regulators of autophagy and the cell cycle in arsenic-induced hepatic toxicity via real-time RT-PCR array analysis in livers of NMRI mice exposed to an environmentally relevant and minimally cytotoxic concentration of arsenite (50 ppm) in drinking water while being fed with HFD for 20 weeks. We examined Bax, p27Kip, p16INK4a, Pten, Rb1, Trp53, and Tgfb1 as co-regulators of autophagy and the cell cycle. Overall, as shown by the results of this study, HFD uptake decreased the expression of co-regulators of autophagy and the cell cycle. Arsenic uptake not only offsets this reduction but also in the group that received both arsenic and HFD simultaneously, leading to increased expression of all genes that affect cell cycle arrest. In conclusion, these results demonstrate activation of the cell cycle control system in the liver of mice exposed to arsenic and HFD, mainly involving the participation of co-regulators of autophagy and the cell cycle.

Keywords

• Autophagy
• Cell cycle
• HFD
• Arsenic
• p27Kip1
• p16INK4a