Introduction: In this study, we focus on the different aspects of the cross-regulation of autophagy and the cell cycle during nutritional and environmental stress. The relationship between autophagy, cell cycle arrest and related mechanisms is not yet well understood. In response to stressful conditions, cells are capable of 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. Like cell cycle arrest, autophagy is induced or inhibited in response to different stressful conditions and plays a key role in protecting the cell. In our previous study, it was shown that the exposure to arsenic and
HFD resulted in the upregulation of autophagy (1,2,3,4). Methods: Therefore, in this study, we utilized 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 a
HFD for 20 weeks. Results:
Cell cycle arrest often relies on the function of cell cycle inhibitors. In this study, we examined Cdkn1b (p27Kip1), Cdkn2a (p16INK4a) and Rb1 (Retinoblastoma) as co-regulators of autophagy and the cell cycle. In the
HFD recipient group the expression of p27Kip1,
p16INK4a and Rb1 genes decreased. In the LFD-As recipient group the expression of the Rb1 increased, but both
p16INK4a and
p27Kip1 showed reduced expression. In the HFD-As recipient group the expression of p27Kip1,
p16INK4a and Rb1 genes increased. Conclusion: Overall, the results of this study indicate that arsenic affects Rb expression.
HFD uptake resulted in decreased expression of genes 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 three genes that affect cell cycle arrest. In conclusion, these results demonstrate an activation of the cell cycle control system in hepatocytes of mice exposed to arsenic and HFD, mainly involving the participation of p27Kip1,
p16INK4a and Rb.