Publications (2)5.15 Total impact
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Article: The role of the IRE1 pathway in PBDE-47-induced toxicity in human neuroblastoma SH-SY5Y cells in vitro.
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ABSTRACT: Polybrominated diphenyl ethers (PBDEs) are widely used as flame retardants. As one of the dominant congeners, 2,2', 4,4'-tetrabromodiphenyl ether (PBDE-47) has been shown to be neurotoxic to neuronal cells although the mechanisms remain unclear. To test whether PBDE-47's toxicity was related to endoplasmic reticulum (ER) stress and the unfolded protein response (UPR), human neuroblastoma cells (SH-SY5Y cells) were treated with different concentrations of PBDE-47. Reactive oxygen species (ROS), apoptosis and the expressions of the inositol-requiring enzyme 1 (IRE1) pathway-related molecules were detected. PBDE-47 exposure increased ROS production and activated the UPR by increasing the expressions of glucose-regulated protein 78 (GRP78), IRE1, X-box-binding protein-1 (XBP1), phosphorylation of c-jun N-terminal kinase (JNK) and GADD153/C/EBP homologous protein (CHOP) genes in SH-SY5Y cells. The apoptotic rate increased with the remarkable up-regulation of the Bax/Bcl-2 ratio after IRE1 knockdown, demonstrating the anti-apoptotic role of IRE1. Furthermore, the expressions of CHOP, XBP1 and JNK were down-regulated indicating that IRE1 may activate these key molecules related to apoptosis. PBDE-47 exposure can increase ROS production and activate the IRE1 pathway of the UPR in SH-SY5Y cells contributing to its toxicity. The IRE1 pathway may have both protective and proapoptotic effects on SH-SY5Y cells.Toxicology Letters 04/2012; 211(3):325-33. · 3.23 Impact Factor -
Article: The Effect of c-Fos Demethylation on Sodium Fluoride-induced Apoptosis in L-02 Cells.
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ABSTRACT: To investigate the effects of sodium fluoride (NaF) on apoptosis, c-Fos mRNA and protein expression levels, and methylation status as well as Dnmt1, Dnmt3a, and Dnmt3b mRNA expression levels in human embryo hepatocyte (L-02) which were exposed to different concentrations of NaF (0, 20, 40, and 80 mg/l) for 24 h in vitro. Results showed that the percentage of apoptosis and c-Fos mRNA and protein expression levels in 40 and 80 mg/l NaF-treated groups were higher than those in the control group (P < 0.05). Further, Dnmt1 mRNA expression level was significantly decreased in the 80 mg/l NaF-treated groups compared to the control group (P < 0.05); Dnmt3a and Dnmt3b mRNA expression levels were significantly decreased in 40 and 80 mg/l NaF-treated groups compared to the control group (P < 0.05). c-Fos methylation levels, according to the bisulfite sequencing results, were decreased in 20, 40, and 80 mg/l NaF-treated groups against the control group. These results suggest that NaF could induce apoptosis and upregulate mRNA and protein expression level of c-Fos as well as decrease mRNA expression levels of Dnmt1, Dnmt3a, and Dnmt3b in L-02 cells. The decrease in c-Fos methylation levels might be involved in the early phase of apoptosis induced by NaF in L-02 cells.Biological trace element research 04/2012; 149(1):102-9. · 1.92 Impact Factor
