کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5850451 | 1561782 | 2013 | 8 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Involvement of the mitochondrial p53 pathway in PBDE-47-induced SH-SY5Y cells apoptosis and its underlying activation mechanism Involvement of the mitochondrial p53 pathway in PBDE-47-induced SH-SY5Y cells apoptosis and its underlying activation mechanism](/preview/png/5850451.png)
- 2,2â²,4,4â²-tetrabromodiphenyl ether-elicited SH-SY5Y cells apoptosis contributes to cell death and neurotoxicity.
- Mitochondrial damage and p53 pathway are involved in 2,2â²,4,4â²-tetrabromodiphenyl ether-induced SH-SY5Y cells apoptosis.
- 2,2â²,4,4â²-tetrabromodiphenyl ether-exerted p53 activation and neuron death is independent on p53 promoter demethylation.
2,2â²,4,4â²-tetrabromodiphenyl ether (PBDE-47)-elicited neurotoxicity is associated with neural apoptosis; however the underlying mechanisms remain unclear. To investigate whether the mitochondrial p53 pathway is involved in neuronal apoptosis induced by PBDE-47 and to correlate DNA hypomethylation with p53 activation, human neuroblastoma (SH-SY5Y) cells were treated with different concentrations of PBDE-47 (1, 5, 10 μmol/L) for 24 h in vitro. The apoptosis and ultrastructural alterations in cells, levels of p53, Bcl-2, Bax, cytochrome c (Cyt c), caspase-3 and methylation status of p53 promoter were determined. Hoechst 33258 staining and transmission electron microscopy analysis showed that PBDE-47 induced SH-SY5Y cells apoptosis characterized by the typical apoptotic morphological changes. In addition, PBDE-47 activated the p53-dependent mitochondrial apoptotic pathway as evidenced by up-regulation of p53 and Bax, down-regulation of Bcl-2 and Bcl-2/Bax ration, enhancement of Cyt c release from mitochondria into the cytosol, activation of caspase-3 as well as ultrastructural abnormalities of mitochondria. However, no obvious decrease in p53 promoter methylation levels was observed in any of the treatment groups by bisulfite genomic sequencing. Collectively, these results suggest that the mitochondrial p53 pathway is involved in PBDE-47-induced SH-SY5Y cells apoptosis, nevertheless p53 promoter hypomethylation may not be implicated in this process.
Journal: Food and Chemical Toxicology - Volume 62, December 2013, Pages 699-706