Department

neurobiology

Document Type

Article

Abstract

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.

Publication Date

5-2-2003

Publication Title

Journal of Biological Chemistry

ISSN

00219258

Volume

278

Issue

18

First Page

15633

Last Page

15640

Digital Object Identifier (DOI)

10.1074/jbc.M210389200

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