The role of Fas/FasL pathway in apoptosis of rat nerve cells induced by arsenic exposure

Objective To study the expression of Fas, FasL, FADD, cysteinyl aspartate specific proteinase (caspase)-8 and caspase-3 in rat brain cortex under chronic arsenic exposure, in order to explore the possible mechanism of nerve cell apoptosis under arsenic exposure. Methods Forty SD rats were randomly assigned to four treatment groups with equal number in each group according to body weight. Control group was given distilled water while low-, medium-and high-dose groups were given sodium arsenite solution in concentrations of 5, 10 and 50 mg/L, respectively. After exposed to sodium arsenite for three months, terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) was used to detect the apoptosis positive nerve cells; real-time PCR was used to detect the mRNA expression level of Fas, FasL and FADD; immunohistochemical and Western blotting were used to test the protein expression level; caspase kits was used to detect the activity of caspase-8 and caspase-3. Results ① According to the results of TUNEL: for control, low-, medium-and high-dose groups, their apoptotic cell rates were (15.50 ± 9.85)%, (16.75 ± 10.01)%, (36.75 ± 14.73)% and (50.50 ± 19.16)%; low-, medium-and high-dose groups were significantly higher than control group (all P 0.05); FADD were 0.77 ± 0.23, 0.80 ± 0.13, 0.97 ± 0.15 and 0.98 ± 0.25, respectively, for control, low-, medium-and high-dose groups; a significant rise was found in medium-and high-dose groups than the control group (all P 0.05); FADD were 5.01 ± 1.00, 7.10 ± 1.84, 6.04 ± 1.51 and 7.36 ± 1.32, respectively, for control, low-, medium-and high-dose groups; low-, high-dose groups were higher than control group statistically (all P 0.05); FADD were (17.03 ± 7.34)%, (17.27 ± 5.03)%, (18.68 ± 6.56)% and (24.13 ± 7.25)%, respectively, for control, low-, medium-and high-dose groups; high-dose group was significantly higher than control group (P < 0.05). ⑤ The caspase-8 activity for the four groups were (3.07 ± 0.69), (4.39 ± 1.32), (4.51 ± 0.83), (4.67 ± 1.36) U/g, respectively; low-, medium-and high-dose groups were significantly higher than control group (all P < 0.05); the caspase-3 activity of the above four groups were (2.84 ± 0.36), (3.65 ± 1.38), (4.23 ± 0.99), (4.41 ± 1.02) U/g; medium-and high-dose groups were significantly higher than control group (all P < 0.05). Conclusion The expression of Fas and FADD and activity of caspase-8 and caspase-3 in rat cortex are increased significantly under chronic arsenic exposure, which may be related to the apoptosis of nerve cells due to arsenic exposure through the Fas/FasL signal transduction pathway. Key words: Arsenic poisoning; Apoptosis; Fas/FasL