Effects of PM2.5 exposure on clock gene BMAL1 and cell cycle in human umbilical vein endothelial cells.

Abstract

Background: Fine particulate matter (PM_2.5) exposure has been closely associated with cardiovascular diseases, which are relevant to cell cycle arrest. Brain and muscle aryl-hydrocarbon receptor nuclear translocator-like protein 1 (BMAL1) not only participates in regulating the circadian clock but also plays a role in modulating cell cycle. However, the precise contribution of the circadian clock gene BMAL1 to PM_2.5-induced cell cycle change remains unclear. This study aims to explore the impact of PM_2.5 exposure on BMAL1 expression and the cell cycle in human umbilical vein endothelial cells (HUVECs).

Methods: HUVECs was exposed to PM_2.5 for 24 hours at different concentrations ((0, 12.5, 25, 75 and 100 μg.mL-1) to elucidate the potential toxic mechanism. Following exposure to PM_2.5, cell viability, ROS, cell cycle, and the expression of key genes and proteins were detected.

Results: A remarkable decrease in cell viability is observed in the PM_2.5-exposed HUVECs, as well as a significant increase in ROS production. In addition, PM_2.5-exposed HUVECs have cycle arrest in G0/G1 phase, and the gene expression of p27 is also markedly increased. The protein expression of BMAL1 and the gene expression of BMAL1 are increased significantly. Moreover, the protein expressions of p-p38 MAPK and p-ERK1/2 exhibit a marked increase in the PM_2.5-exposed HUVECs. Furthermore, following the transfection of HUVECs with siBMAL1 to suppress BMAL1 expression, we observed a reduction in both the protein and gene expression of the MAPK/ERK pathway in HUVECs exposed to PM_2.5.

Conclusions: Overall, our results indicate that PM_2.5 exposure significantly upregulates the circadian clock gene expression of BMAL1 and regulates G0/G1 cell cycle arrest in HUVECs through the MAPK/ERK pathway, which may provide new insights into the potential molecular mechanism regarding BMAL1 on PM_2.5-induced cardiovascular diseases.