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 micromol/L) and/or PCB153 (5 micromol/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.
He
Ping
P
Department of Environmental Health and MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, PR China.
Wang
Ai-Guo
AG
Xia
Tao
T
Gao
Ping
P
Niu
Qiang
Q
Guo
Li-Juan
LJ
Xu
Ba-Yi
BY
Chen
Xue-Min
XM
D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000032:analysis; D002118:Calcium / Q000032:analysis; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000032:analysis; D053454:Caspase 12 / Q000032:analysis; D053148:Caspase 3 / Q000032:analysis; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects*; D002478:Cells, Cultured; D045304:Cytochromes c / Q000032:analysis; D064550:Death-Associated Protein Kinases; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D055768:Halogenated Diphenyl Ethers / Q000633:toxicity*; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D009474:Neurons / Q000737:chemistry / Q000187:drug effects*; D011075:Polybrominated Biphenyls; D011078:Polychlorinated Biphenyls / Q000633:toxicity*
D051017:Apoptosis Regulatory Proteins; D055768:Halogenated Diphenyl Ethers; D011075:Polybrominated Biphenyls; C511295:2,2',4,4'-tetrabromodiphenyl ether; D045304:Cytochromes c; D011078:Polychlorinated Biphenyls; D007770:L-Lactate Dehydrogenase; D064550:Death-Associated Protein Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D053454:Caspase 12; D053148:Caspase 3; D002118:Calcium; C014024:2,4,5,2',4',5'-hexachlorobiphenyl