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

Environ Toxicol. 2011 Feb;26(1):86-92. doi: 10.1002/tox.20543.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects*
  • Brain Neoplasms / enzymology
  • Brain Neoplasms / metabolism
  • Caspase 3 / genetics
  • Caspase 3 / metabolism
  • Caspase 8 / genetics
  • Caspase 8 / metabolism
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Fas Ligand Protein / genetics
  • Fas Ligand Protein / metabolism*
  • Humans
  • Nervous System / drug effects
  • Neuroblastoma / enzymology
  • Neuroblastoma / metabolism
  • RNA, Messenger / metabolism
  • Signal Transduction / drug effects*
  • Sodium Fluoride / toxicity*
  • Trace Elements / toxicity*
  • fas Receptor / genetics
  • fas Receptor / metabolism*

Substances

  • Fas Ligand Protein
  • RNA, Messenger
  • Trace Elements
  • fas Receptor
  • Sodium Fluoride
  • Caspase 3
  • Caspase 8