Oxidative stress-elicited autophagosome accumulation contributes to human neuroblastoma SH-SY5Y cell death induced by PBDE-47

Polybrominated diphenyl ethers, a ubiquitous persistent organic pollutant used as brominated flame retardants, is known to damage nervous system, however the underlying mechanism is still elusive. In this study, we used human neuroblastoma SH-SY5Y cells to explore the effects of PBDE-47 on autophagy and investigate the role of autophagy in PBDE-47-induced cell death. Results showed PBDE-47 could increase autophagic level (performation of cell ultrastructure with double membrane formation, MDC-positive cells raised, autophagy-related proteins LC3-II, Beclin1 and P62 increased) after cells exposed to PBDE-47. Then cells were exposed to PBDE-47 (1, 5, 10 μmol/L) respectively for 1, 3, 6, 9, 12, 18, 24 h, and the results showed that PBDE-47 increased the levels of LC3-II, Beclin1 and P62 in 5, 10 μmol/L (9, 12, 18, 24 h) PBDE-47 exposed groups. Furthermore, ROS scavenger N-Acetyl-l-cysteine (NAC), autophagic inhibitor 3-methyladenine (3-MA) and 5 μmol/L PBDE-47 treated for 9 h and 24 h were chosen for the follow-up research. Moreover, 3-MA significantly improved cell viability when cells exposed to 5 and 10 μmol/L PBDE-47, indicating that PBDE-47-induced autophagic cell death. Importantly, NAC could decrease PBDE-47-induced LC3-II, Beclin1 and P62 expression. We concluded that autophagosome accumulation mediated by oxidative stress may contribute to SH-SY5Y cell death induced by PBDE-47.