Benzo[a]pyrene induces pyroptotic and autophagic death through inhibiting PI3K/Akt signaling pathway in HL-7702 human normal liver cells

Qingshu Li, Chunxia Gao, Hong Deng, Quancai Song, Li Yuan
Journal of Toxicological Sciences 2019, 44 (2): 121-131
Benzo(α)pyrene (BaP) possesses a forceful hepatotoxicity, and is ubiquitous in foods and ambient air. Our previous study found that BaP induced pyroptotic and autophagic death in HL-7702 human liver cells; the relevant mechanisms, however, remain unknown. This work was therefore to unravel the effects of the PI3K/Akt signaling pathway on pyroptotic and autophagic death triggered by BaP. Cells were treated with or without LY294002 (PI3K/Akt inhibitor) and IGF-1 (PI3K/Akt activator) before BaP exposure, and the results showed that compared with the control, the protein expression of p-Akt was markedly decreased by BaP (p < 0.05). IGF-1 did not subvert this inhibitive effect of BaP, while LY294002 enhanced it. Furthermore, the protein expression of pyroptosis (Cleaved Caspase-1, NO, IL-1β, IL-18), as well as LDH and the relative electrical conductivity were significantly augmented by BaP. The levels of these indices were increased by LY294002 pretreatment, and decreased by IGF-1. Similarly, LY294002 enhanced BaP-induced increase in the key protein expression of autophagy (Beclin-1 and LC3II), while IGF-1 weakened it. Finally, the phosphorylation of FOXO4 was clearly (p < 0.01) inhibited by BaP, and LY294002 suppressed this inhibitive effect of BaP, while IGF-1 strengthened it. In conclusion, BaP was able to induce pyroptotic and autophagic death via blocking the PI3K/Akt signaling pathway in HL-7702 liver cells.

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