Effects of the Fas/Fas‐L pathway on fluoride‐induced apoptosis in SH‐SY5Y cells

• DOI: 10.1002/tox.20543
• Publication Date: 2009-10-22T19:39:51Z
• Authors: Bayi Xu; Zhixia Xu; Tao Xia; Ping He; Ping Gao; Weihong He; Ming Zhang; Lijuan Guo; Qiang Niu; Aiguo Wang
• Keywords: 0301 basic medicine; Caspase 8; 0303 health sciences; Fas Ligand Protein; Dose-Response Relationship, Drug; Brain Neoplasms; Caspase 3; Cell Survival; Apoptosis; Nervous System; Trace Elements; 3. Good health; Neuroblastoma; 03 medical and health sciences; Cell Line, Tumor; Humans; Sodium Fluoride; RNA, Messenger; fas Receptor; Signal Transduction

AbstractThe 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. © 2009 Wiley Periodicals, Inc. Environ Toxicol 26: 86–92, 2011.