Chen Hongmei, Tang Xuexi, Zhou Bin, Xu Ningning, Zhou Zhongyuan, Fang Kuan, Wang You
Department of Marine Ecology, College of Marine Life Sciences, Ocean University of China, Qingdao 266003, China.
Department of Marine Ecology, College of Marine Life Sciences, Ocean University of China, Qingdao 266003, China.
Environ Toxicol Pharmacol. 2017 Mar;50:76-82. doi: 10.1016/j.etap.2016.12.009. Epub 2016 Dec 21.
Cell proliferation is closely related to cell cycle which is strictly regulated by genes and regulatory proteins. In the present study, we comparatively analyzed the toxic effects of BDE-47 and BDE-209 on cell proliferation of Neuro-2a cells, and the possible mechanism was discussed. The results indicated that BDE-47 significantly inhibited the cell proliferation and the cell cycle were arrest at G1 phase, while BDE-209 had little effects on either cell proliferation or cell cycle. qRT-PCR and Western blot assay presented that BDE-47 up-regulated the gene expressions of p53 and p21, which down-regulated the expresseion of cyclinD1 and CDK2, and inhibited retinoblastoma protein (pRb) phosphorylation. This process could effectively arrest the cell cycle at G1 phase, which finally caused the inhibition on Neuro-2a cell proliferation. However, BDE-209 was only up-regulated the gene expressions of p53, also suggested to be involved in the inhibition on Neuro-2a cell proliferation.
细胞增殖与细胞周期密切相关，细胞周期受到基因和调节蛋白的严格调控。在本研究中，我们比较分析了BDE-47和BDE-209对Neuro-2a细胞增殖的毒性作用，并探讨了其可能的机制。结果表明，BDE-47显著抑制细胞增殖，细胞周期阻滞在G1期，而BDE-209对细胞增殖和细胞周期均无明显影响。qRT-PCR和Western blot分析表明，BDE-47上调p53和p21的基因表达，下调细胞周期蛋白D1（cyclinD1）和细胞周期蛋白依赖性激酶2（CDK2）的表达，并抑制视网膜母细胞瘤蛋白（pRb）的磷酸化。这一过程可有效将细胞周期阻滞在G1期，最终导致Neuro-2a细胞增殖受到抑制。然而，BDE-209仅上调p53的基因表达，也提示其参与了对Neuro-2a细胞增殖的抑制作用。
