TY - JOUR
T1 - Nicotine modulates the expression of a diverse set of genes in the neuronal SH-SY5Y cell line
AU - Dunckley, Travis
AU - Lukas, Ronald J.
PY - 2003/5/2
Y1 - 2003/5/2
N2 - Nicotine exposure can have long lasting effects on nervous system function, some of which must contribute to nicotine dependence. Up-regulation, an increase in numbers of radioligand-binding nicotinic acetylcholine receptors (nAChR), occurs on exposure to nicotine at high concentrations. To determine whether altered gene expression might account for long term changes and up-regulation following nicotine exposure, we assessed effects of 1 h of 1 mM nicotine exposure on alter. ation of gene expression in the neuron-like SH-SY5Y neuroblastoma clonal line. Repeat and cross-controlled microarray analyses yielded a list of 17 genes from the initially screened ∼5,000 whose expression was consistently altered following nicotine treatment. Subsequent quantitative, real time reverse transcriptase PCR analyses confirmed altered expression in 14 of 16 genes tested. Further, the general nAChR antagonist, d-tubocurarine, blocked all but two of the observed changes in gene expression, indicating that these changes are dependent on nAChR activation. Use of other antagonists revealed that nAChR subtypes can differentially affect gene expression. The genes affected code for proteins that may be broadly categorized into four groups: transcription factors, protein processing factors, RNA-binding proteins, and plasma membrane-associated proteins. Our results suggest that nicotinic activation of nAChR may have a broad role in affecting cellular physiology through modulating gene expression.
AB - Nicotine exposure can have long lasting effects on nervous system function, some of which must contribute to nicotine dependence. Up-regulation, an increase in numbers of radioligand-binding nicotinic acetylcholine receptors (nAChR), occurs on exposure to nicotine at high concentrations. To determine whether altered gene expression might account for long term changes and up-regulation following nicotine exposure, we assessed effects of 1 h of 1 mM nicotine exposure on alter. ation of gene expression in the neuron-like SH-SY5Y neuroblastoma clonal line. Repeat and cross-controlled microarray analyses yielded a list of 17 genes from the initially screened ∼5,000 whose expression was consistently altered following nicotine treatment. Subsequent quantitative, real time reverse transcriptase PCR analyses confirmed altered expression in 14 of 16 genes tested. Further, the general nAChR antagonist, d-tubocurarine, blocked all but two of the observed changes in gene expression, indicating that these changes are dependent on nAChR activation. Use of other antagonists revealed that nAChR subtypes can differentially affect gene expression. The genes affected code for proteins that may be broadly categorized into four groups: transcription factors, protein processing factors, RNA-binding proteins, and plasma membrane-associated proteins. Our results suggest that nicotinic activation of nAChR may have a broad role in affecting cellular physiology through modulating gene expression.
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U2 - 10.1074/jbc.M210389200
DO - 10.1074/jbc.M210389200
M3 - Article
C2 - 12588870
AN - SCOPUS:0038521299
SN - 0021-9258
VL - 278
SP - 15633
EP - 15640
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 18
ER -