Decabromodiphenyl ether（BDE-209） is a prevalent polybrominated diphenyl ether（PBDE）congener known to have neurotoxicity. Effects of BDE-209 on Neuro-2a cells were performed in the present study and the possible ap...Decabromodiphenyl ether（BDE-209） is a prevalent polybrominated diphenyl ether（PBDE）congener known to have neurotoxicity. Effects of BDE-209 on Neuro-2a cells were performed in the present study and the possible apoptotic pathway was discussed. Results indicated that BDE-209 induced Neuro-2a cell apoptosis, increased the protein expression of Fas and Fas-associated death domain-containing protein（FADD） and activated the caspase-8 and-3activities in a concentration-dependent manner, inferring the death-receptor pathway was involved in the apoptotic process. Meanwhile, BDE-209 exposure increased the Bax/Bcl-2 ratio and decreased the cellular mitochondrial membrane potential（MMP） which led to cytochrome C released to the cytoplasm. The intracellular caspase-9 was elevated simultaneously,which caused downstream caspase cascade and triggered cell apoptosis. Moreover, BDE-209 exposure increased cellular reactive oxygen species（ROS） level in a concentration-dependent manner and the addition of N-acetyl-L-cysteine（NAC）, known as ROS scavengers, obviously reduced the apoptotic rate and a positive relationship was observed between the degree of apoptosis blocking and the loss of MMP and ROS production. We thus concluded that BDE-209 induced Neuro-2a cell apoptosis via the combination of the death-receptor signaling pathway and the mitochondrial signaling pathway. The elevated ROS production was considered to magnify the intracellular apoptosis signal and played a crucial role in apoptosis of Neuro-2a cells induced by BDE-209.展开更多
基金supported by the National Natural Science Foundation of China(Nos.41476109 and 41276140)the Joint Fund of the National Natural Science Foundation of China and Shandong Province(No.NSFC-U 1406403)
文摘Decabromodiphenyl ether（BDE-209） is a prevalent polybrominated diphenyl ether（PBDE）congener known to have neurotoxicity. Effects of BDE-209 on Neuro-2a cells were performed in the present study and the possible apoptotic pathway was discussed. Results indicated that BDE-209 induced Neuro-2a cell apoptosis, increased the protein expression of Fas and Fas-associated death domain-containing protein（FADD） and activated the caspase-8 and-3activities in a concentration-dependent manner, inferring the death-receptor pathway was involved in the apoptotic process. Meanwhile, BDE-209 exposure increased the Bax/Bcl-2 ratio and decreased the cellular mitochondrial membrane potential（MMP） which led to cytochrome C released to the cytoplasm. The intracellular caspase-9 was elevated simultaneously,which caused downstream caspase cascade and triggered cell apoptosis. Moreover, BDE-209 exposure increased cellular reactive oxygen species（ROS） level in a concentration-dependent manner and the addition of N-acetyl-L-cysteine（NAC）, known as ROS scavengers, obviously reduced the apoptotic rate and a positive relationship was observed between the degree of apoptosis blocking and the loss of MMP and ROS production. We thus concluded that BDE-209 induced Neuro-2a cell apoptosis via the combination of the death-receptor signaling pathway and the mitochondrial signaling pathway. The elevated ROS production was considered to magnify the intracellular apoptosis signal and played a crucial role in apoptosis of Neuro-2a cells induced by BDE-209.
