Mechanism of the neurotoxic effect of PBDE-47 and interaction of PBDE-47 and PCB153 in enhancing toxicity in SH-SY5Y cells

Polybrominated diphenyl ethers (PBDEs) are used in large quantities as flame-retardant additives, especially in electrical appliances and textiles. Because of their structural similarity, PBDEs are thought to have toxicities similar to those of polychlorinated biphenyls (PCBs), which are well-known persistent compounds. Both 2,2',4,4'-tetrabromodiphenyl ether (PBDE-47) and 2,2',4,4',5, 5'-hexachlorobiphenyl (PCB153) can coexist in the environment and human tissues as dominant congeners of PBDEs and PCBs, respectively. To explore the mechanisms of the neurotoxic effect of PBDE-47 and the interaction in combination with PCB153, cell viability, lactate dehydrogenase (LDH) leakage, intracellular Ca2+ concentration ([Ca2+](i)), apoptosis and expression levels of death associated protein kinase (DAPK), caspase3, caspase12 and cytochrome c mRNA and proteins were measured in SH-SY5Y cells treated with PBDE-47 (0,1, 5,10 mu mol/L) and/or PCB153 (5 mu mol/L) for 24 h. Compared to controls, the cell viabilities were clearly decreased (P < 0.05), and LDH leakage, [Ca2+](i) and apoptosis were significantly increased (P < 0.05). Furthermore, expression levels of DAPK and caspase3 mRNA, caspase12, as well as cytochrome c mRNA and proteins were markedly increased (P < 0.05), while pro-caspase3 proteins were significantly decreased (P < 0.05). A positive correlation between [Ca2+](i) and percentage of apoptotic cells (r = 0.86, P < 0.05) and an interaction between PBDE-47 and PCB153 (P < 0.05) were observed. We conclude that PBDE-47 can induce SH-SY5Y cell apoptosis via three classic apoptosis pathways and interact with PCB153 to enhance neurotoxicity. (C) 2008 Elsevier Inc. All rights reserved.