MOE Key Lab of Environment and Health, Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030, Hubei, People's Republic of China.
Environ Toxicol. 2011 Feb;26(1):86-92. doi: 10.1002/tox.20543.
The mechanisms underlying fluoride-induced apoptosis in neurons still remain unknown. To investigate apoptosis, caspase-3 activity, and mRNA expression of Fas, Fas-L, and caspases (-3 and -8) induced by fluoride, human neuroblastoma (SH-SY5Y) cells were incubated with 0, 20, 40, and 80 mg/L sodium fluoride (NaF) for 24 h in vitro. The data show that cell viability in the 40 and 80 mg/L fluoride groups were significantly lower than that of the control group. The percentages of apoptosis in the 40 and 80 mg/L fluoride groups were markedly higher than those in the control group, and they increased with the increase in fluoride concentration. The activity of caspase-3 and mRNA expression levels for Fas, Fas-L, and caspases (-3 and -8) in the 40 and 80 mg/L fluoride groups were significantly higher than those in the control group. An agonistic anti-Fas monoclonal antibody (CH-11) significantly augmented apoptosis induction by fluoride, showing a synergistic effect, while a Fas-blocking antibody (ZB4) partly inhibited fluoride-induced apoptosis of SH-SY5Y cells. The results indicate that fluoride exposure could induce apoptosis in SH-SY5Y cells, and the Fas/Fas-L signaling pathway may play an important role in the process.
氟化物诱导神经元细胞凋亡的机制尚不清楚。为了研究氟化物诱导的细胞凋亡、半胱氨酸天冬氨酸蛋白酶-3（caspase-3）活性以及 Fas、FasL 和 caspase-3、caspase-8 的 mRNA 表达，将人神经母细胞瘤（SH-SY5Y）细胞在体外分别用 0、20、40 和 80mg/L 氟化钠（NaF）孵育 24h。结果显示，40 和 80mg/L 氟化物组的细胞活力明显低于对照组，40 和 80mg/L 氟化物组的细胞凋亡率明显高于对照组，且随着氟化物浓度的增加而增加。40 和 80mg/L 氟化物组 caspase-3 的活性和 Fas、FasL 及 caspase-3、caspase-8 的 mRNA 表达水平明显高于对照组。激动型抗 Fas 单克隆抗体（CH-11）显著增强了氟化物诱导的细胞凋亡，表现出协同作用，而 Fas 阻断抗体（ZB4）部分抑制了氟化物诱导的 SH-SY5Y 细胞凋亡。结果表明，氟化物暴露可诱导 SH-SY5Y 细胞凋亡，Fas/FasL 信号通路可能在该过程中发挥重要作用。
