Oxidative stress might be a mechanism connected with the decreased alpha 7 nicotinic receptor influenced by high-concentration of fluoride in SH-SY5Y neuroblastoma cells.
The possible mechanism concerning decreased alpha 7 nicotinic acetylcholine receptor (nAChR) influenced by fluorosis was investigated. SH-SY5Y cells were exposed to fluoride within the range of 0.05-5 mM [corrected] or ferrous iron (1-100 mM) [corrected] a free radical inducer. The levels of alpha 7 nAChR expression, lipid peroxidation and protein oxidation were detected. The results showed that both high-concentrations of fluoride and ferrous iron induced increased levels of lipid peroxidation and protein oxidation in SH-SY5Y cells with concentration-dependent manners. In addition, inhibition of alpha 7 nAChR at protein level was observed in the cells exposed to high amounts of fluoride or ferrous iron. Furthermore, a declined value of Bmax in [125I]alpha-bungarotoxin binding sites was found in the cells treated with the high-concentration of fluoride. Interestingly, antioxidants (vitamin E and glutathione) can attenuate the inhibition of the receptor induced by fluoride. These findings suggest that oxidative stress resulted from fluorosis might directly induce the deficit of alpha 7 nAChR.
Gao
Qin
Q
Department of Pathology, Guiyang Medical University, Guiyang 550004, Guizhou, PR China.
Liu
Yan-Jie
YJ
Guan
Zhi-Zhong
ZZ
D000975:Antioxidants / Q000494:pharmacology; D002038:Bungarotoxins / Q000378:metabolism; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D005296:Ferrous Compounds / Q000008:administration & dosage / Q000494:pharmacology; D015870:Gene Expression; D005978:Glutathione / Q000494:pharmacology; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D009447:Neuroblastoma / Q000378:metabolism* / Q000473:pathology; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects*; D011978:Receptors, Nicotinic / Q000187:drug effects* / Q000378:metabolism; D012969:Sodium Fluoride / Q000008:administration & dosage / Q000633:toxicity*; D014810:Vitamin E / Q000494:pharmacology; D064569:alpha7 Nicotinic Acetylcholine Receptor
D000975:Antioxidants; D002038:Bungarotoxins; C579167:Chrna7 protein, human; D005296:Ferrous Compounds; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; D014810:Vitamin E; D012969:Sodium Fluoride; D005978:Glutathione