Title

Nicotinic Modulation Of Gene Expression In Sh-Sy5Y Neuroblastoma Cells

Department

neurobiology

Document Type

Article

Abstract

Exposure to nicotine has a broad range of physiological and psychological effects that can be long lasting and contribute to nicotine dependence. On a time course longer than that needed to activate nicotinic acetylcholine receptor (nAChR) function, nicotine exposure induces functional inactivation of nAChR, upregulation of nAChR radioligand binding sites, and other alterations of cellular functions. To identify possible mechanisms underlying nicotine-induced changes in nAChR numbers and function, we defined changes in gene expression in neuron-like, SH-SY5Y human neuroblastoma cells following 24 h of continuous exposure to 1 mM nicotine. This treatment condition produces both functional inactivation and upregulation of nAChR. Repeat and cross-controlled microarray (∼ 5000 genes queried) analyses revealed 163 genes whose expression was consistently altered at the p < 0.01 level following nicotine treatment. Quantitative, real-time, reverse transcription-polymerase chain reaction analyses confirmed altered expression of thirteen out of fourteen of these genes chosen for further study, including contactin 1, myozenin 2, and ubiquitin-conjugating enzymes E2C and E2S. Inhibition or reversal of these effects by the general nAChR antagonist, d-tubocurarine, indicated that gene expression changes are dependent on nAChR activation. Studies using other nAChR subtype-selective antagonists identified gene expression changes that required activation of both α7- and α3*-nAChR, α7-nAChR alone, or either α7- or α3β4*-nAChR, suggesting some convergent and some divergent pathways of gene activation coupled to these nAChR subtypes. These results suggest that longer-term physiological and psychological effects of nicotine exposure and changes in nAChR expression may be due in part to effects on gene expression initiated by interactions with nAChR. © 2006 Elsevier B.V. All rights reserved.

Publication Date

10-20-2006

Publication Title

Brain Research

ISSN

00068993

Volume

1116

Issue

1

First Page

39

Last Page

49

Digital Object Identifier (DOI)

10.1016/j.brainres.2006.07.111

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