Effects of PM 2.5 exposure on clock gene BMAL1 and cell cycle in human umbilical vein endothelial cells.

BACKGROUND: Fine particulate matter (PM2.5 ) 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 PM2.5 -induced cell cycle change remains unclear. This study aims to explore the impact of PM2.5 exposure on BMAL1 expression and the cell cycle in human umbilical vein endothelial cells (HUVECs).

METHODS: HUVECs was exposed to PM2.5 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 PM2.5 , 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 PM2.5 -exposed HUVECs, as well as a significant increase in ROS production. In addition, PM2.5 -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 PM2.5 -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 PM2.5 .

CONCLUSIONS: Overall, our results indicate that PM2.5 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 PM2.5 -induced cardiovascular diseases.