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Relationship between intracellular Ca 2+ and ROS during fluoride‐induced injury in SH‐SY5Y cells
Author(s) -
Xu Zhixia,
Xu Bayi,
Xia Tao,
He Weihong,
Gao Ping,
Guo Lijuan,
Wang Zhenglun,
Niu Qiang,
Wang Aiguo
Publication year - 2013
Publication title -
environmental toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.813
H-Index - 77
eISSN - 1522-7278
pISSN - 1520-4081
DOI - 10.1002/tox.20721
Subject(s) - fluoride , egta , chemistry , bapta , sh sy5y , calcium , nuclear chemistry , sodium fluoride , extracellular , reactive oxygen species , intracellular , antioxidant , chelation , biochemistry , inorganic chemistry , cell culture , neuroblastoma , organic chemistry , biology , genetics
The mechanisms underlying the neurotoxicology of endemic fluorosis still remain obscure. To explore lactate dehydrogenase (LDH) leakage, intracellular Ca 2+ concentration ([Ca 2+ ] i ) and reactive oxygen species (ROS) production induced by fluoride, human neuroblastoma (SH‐SY5Y) cells were incubated with sodium fluoride (NaF, 20, 40, 80 mg/L) for 24 h, with 40 mg/L NaF for 3, 6, 12, 18, 24 h, and N ‐acetyl‐ L ‐cysteine (NAC), ethyleneglycol‐bis‐(β‐aminoethyl ether)‐ N , N , N ′, N ′‐tetraacetic acid (EGTA), 1,2‐bis( O ‐aminophenoxy)ethane‐ N , N , N ′, N ′‐tetraacetic acid tetra(acetoxymethyl) ester (BAPTA‐AM) alone or combined with fluoride (40 mg/L) respectively for 12 h in vitro . The results showed that the LDH levels in the 40 and 80 mg/L fluoride‐treated groups were significantly higher than that of the control group (in the test level of 0.05, the difference were statistical significance). [Ca 2+ ] i and ROS reached a peak at 3 h and 12 h respectively after exposure to 40 mg/L fluoride. Fluoride coincubated with NAC (antioxidant) dramatically decreased ROS and LDH levels compared with the fluoride only group (in the test level of 0.05, the difference were statistical significance). However, fluoride‐induced increase in [Ca 2+ ] i was not affected by NAC. BAPTA‐AM (intracellular calcium chelator) markedly lowered fluoride‐induced increase of [Ca 2+ ] i , ROS and LDH levels while EGTA (extracellular calcium chelator) have no effects on them. These results indicate that fluoride‐related Ca 2+ release from the site of intracellular calcium storage causes the elevation of ROS contributing to the cytotoxicity in SH‐SY5Y cells. © 2011 Wiley Periodicals, Inc. Environ Toxicol, 2013.