Protective effects of nicotine against glutamate-induced neurotoxicity in PC12 cells.
This study aimed to assess whether nicotine prevented glutamate neurotoxicity in PC12 cells, and to identify the molecular mechanisms of any effects. The results showed that glutamate neurotoxicity in PC12 cells could be prevented by treatment with nicotine at concentrations of 10 nmol x l(-1) - 1 mmol x l(-1). This effect was in turn found to be inhibited by the application of the nicotinic acetylcholine receptor (nAChR) antagonist mecamylamine. Nicotine significantly decreased the basal level of intracellular free Ca(+2) and enhanced the buffering action on Ca(+2) overload induced by high concentrations of glutamate (5 mmol x l(-1)). In addition, nicotine treatment up-regulated the mRNA and protein expression of apoptosis-related factors including bcl-2 mRNA and protein, but down-regulated the expression of bax mRNA and protein. It is concluded that the protective effects of nicotine against the neurotoxicity induced by glutamate are mediated by nAChRs, due to the increased buffering action on Ca(+2)and the modulation of apoptotic processes.
Sun
Xiulan
X
Beijing Institute of Pharmacology and Toxicology, Beijing 100850, P.R.China.
Liu
Yue
Y
Hu
Gang
G
Wang
Hai
H
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D019254:Genes, bcl-2 / Q000502:physiology; D005971:Glutamates / Q000633:toxicity*; D008464:Mecamylamine / Q000494:pharmacology; D009538:Nicotine / Q000494:pharmacology*; D018733:Nicotinic Antagonists / Q000494:pharmacology; D016716:PC12 Cells; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D051381:Rats; D011978:Receptors, Nicotinic / Q000378:metabolism*; D051028:bcl-2-Associated X Protein
C494828:Bax protein, rat; D005971:Glutamates; D018733:Nicotinic Antagonists; D019253:Proto-Oncogene Proteins c-bcl-2; D011978:Receptors, Nicotinic; D051028:bcl-2-Associated X Protein; D008464:Mecamylamine; D009538:Nicotine; D002118:Calcium