Medicine · 2025
The effects of long-term co-exposure to nanocarbon black particles and benzo[a]pyrene on ROS levels and the AKT/P27 signaling pathway in BEAS-2B cells.
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Zhang Wei, Kong Lingxin, Hu Feng, Li Jiyuan, Ma Shuli, Liang Hong, Wang Mingxia, Li Xingsan, Du Linlin, Li Jiping
Аннотация
BACKGROUND: Long-term co-exposure to nanocarbon black particles (NCBP) and benzo[a]pyrene (B[a]P), as major components of PM2.5, may contribute to respiratory diseases by inducing oxidative damage. However, the molecular mechanisms underlying their synergistic effects remain unclear. This study aimed to investigate the impact of long-term co-exposure to NCBP and B[a]P on reactive oxygen species (ROS) levels and the protein kinase B (AKT)/cyclin-dependent kinase inhibitor 1B (P27) signaling pathway in human bronchial epithelial cells (BEAS-2B) cells.
METHODS: Cytotoxicity concentrations of NCBP and B[a]P for BEAS-2B cells were screened using the cell counting kit-8 assay and applied to subsequent long-term exposure experiments. Intracellular ROS levels were measured via fluorescent probe assay. Western blot was performed to analyze the expression of AKT/P27 pathway-related proteins (phosphatidylinositol 3-kinase, phosphorylated AKT [p-AKT], total AKT, and P27). The regulatory relationship between the pathway and P27 was validated using an AKT inhibitor, and statistical analysis was conducted to evaluate significance.
RESULTS: Significant reductions in cell viability (P < .05) were observed at concentrations of 16 μM B[a]P and 80 μg/mL NCBP. Long-term co-exposure to NCBP and B[a]P-induced ROS accumulation (P < .05). Western blot revealed upregulated p-AKT expression (P < .05) and significant suppression of P27 (P < .05) in the co-exposure group. Inhibition of p-AKT by an AKT inhibitor reversed the downregulation of P27 induced by co-exposure (P < .05), indicating that P27 is a downstream target of the AKT pathway. Compared to single exposures, co-exposure exhibited stronger synergistic effects on oxidative stress dysregulation.
CONCLUSION: Long-term co-exposure to NCBP and B[a]P exacerbates oxidative damage in BEAS-2B cells by activating the AKT signaling pathway, suppressing P27 expression, and promoting ROS accumulation. This study elucidates potential mechanisms of multi-pollutant synergistic effects, providing new insights for health risk assessment of environmental co-exposure.
METHODS: Cytotoxicity concentrations of NCBP and B[a]P for BEAS-2B cells were screened using the cell counting kit-8 assay and applied to subsequent long-term exposure experiments. Intracellular ROS levels were measured via fluorescent probe assay. Western blot was performed to analyze the expression of AKT/P27 pathway-related proteins (phosphatidylinositol 3-kinase, phosphorylated AKT [p-AKT], total AKT, and P27). The regulatory relationship between the pathway and P27 was validated using an AKT inhibitor, and statistical analysis was conducted to evaluate significance.
RESULTS: Significant reductions in cell viability (P < .05) were observed at concentrations of 16 μM B[a]P and 80 μg/mL NCBP. Long-term co-exposure to NCBP and B[a]P-induced ROS accumulation (P < .05). Western blot revealed upregulated p-AKT expression (P < .05) and significant suppression of P27 (P < .05) in the co-exposure group. Inhibition of p-AKT by an AKT inhibitor reversed the downregulation of P27 induced by co-exposure (P < .05), indicating that P27 is a downstream target of the AKT pathway. Compared to single exposures, co-exposure exhibited stronger synergistic effects on oxidative stress dysregulation.
CONCLUSION: Long-term co-exposure to NCBP and B[a]P exacerbates oxidative damage in BEAS-2B cells by activating the AKT signaling pathway, suppressing P27 expression, and promoting ROS accumulation. This study elucidates potential mechanisms of multi-pollutant synergistic effects, providing new insights for health risk assessment of environmental co-exposure.