Effects of the Fas/Fas-L pathway on fluoride-induced apoptosis in SH-SY5Y cells.
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.
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.
Bayi
B
Xu
Zhixia
Z
Xu
Tao
T
Xia
Ping
P
He
Ping
P
Gao
Weihong
W
He
Ming
M
Zhang
Lijuan
L
Guo
Qiang
Q
Niu
Aiguo
A
Wang
D017209:Apoptosis / Q000187:drug effects*; D001932:Brain Neoplasms / Q000201:enzymology / Q000378:metabolism; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D053181:Caspase 8 / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D053222:Fas Ligand Protein / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009420:Nervous System / Q000187:drug effects; D009447:Neuroblastoma / Q000201:enzymology / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D012969:Sodium Fluoride / Q000633:toxicity*; D014131:Trace Elements / Q000633:toxicity*; D019014:fas Receptor / Q000235:genetics / Q000378:metabolism*
D053222:Fas Ligand Protein; D012333:RNA, Messenger; D014131:Trace Elements; D019014:fas Receptor; D012969:Sodium Fluoride; D053148:Caspase 3; D053181:Caspase 8