Decreased nicotinic receptors in PC12 cells and rat brains influenced by fluoride toxicity--a mechanism relating to a damage at the level in post-transcription of the receptor genes.
In order to reveal mechanisms of the decreased nicotinic acetylcholine receptors (nAChRs) resulted from fluoride toxicity, we treated PC12 cells by different concentrations of fluoride (0.1-100 ppm) for 48 h, and exposed rats to high doses of fluoride (30 and 100 ppm) in their drinking water for 7 months. The expression of nAChRs at mRNA and protein levels, neurotoxicity and oxidative stress were analyzed in the study. The results indicated that there were no significant changes at mRNA level of the nAChR alpha3, alpha7, beta2 subunits in PC12 cells, and alpha4, alpha7, beta2 subunits in rat brains between the groups with fluorosis and controls. A significant decline in 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction, and increased levels of protein oxidation and lipid peroxidation were observe in PC12 cells treated with high doses of fluoride or rat brains with chronic fluorosis. The decreases of nAChR alpha3 and alpha7 subunit proteins in PC12 cells resulted from fluoride toxicity were mostly prevented by a pretreatment with antioxidant. The results suggest that the deficit of nAChRs induced by fluoride toxicity occurs at the level of post-transcription of the receptor gene, in which a mechanism might be involved in the damage by oxidative stress.
Shan
Ke-Ren
KR
Department of Molecular Biology, Guiyang Medical College, 550004, Guizhou, PR China.
Qi
Xiao-Lan
XL
Long
Yi-Guo
YG
Nordberg
Agneta
A
Guan
Zhi-Zhong
ZZ
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D015153:Blotting, Western; D001923:Brain Chemistry / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D005459:Fluorides / Q000633:toxicity*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D023282:Nuclease Protection Assays; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects; D016716:PC12 Cells; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D011506:Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D011978:Receptors, Nicotinic / Q000187:drug effects* / Q000235:genetics; D013778:Tetrazolium Salts; D013844:Thiazoles; D014810:Vitamin E / Q000494:pharmacology
D000975:Antioxidants; D011506:Proteins; D012333:RNA, Messenger; D011978:Receptors, Nicotinic; D013778:Tetrazolium Salts; D013844:Thiazoles; D014810:Vitamin E; C022616:thiazolyl blue; D005459:Fluorides