Expression profiling of neural cells reveals specific patterns of ethanol-responsive gene expression

Christelle Thibault, Chaoqiang Lai, Norbert Wilke, Bao Duong, Michael Olive, Sajida Rahman, Helin Dong, Clyde W. Hodge, David J. Lockhart, Michael F. Miles

Research output: Contribution to journalArticle

105 Citations (Scopus)

Abstract

Adaptive changes in gene expression are thought to contribute to dependence, addiction and other behavioral responses to chronic ethanol abuse. DNA array studies provide a nonbiased detection of networks of gene expression changes, allowing insight into functional consequences and mechanisms of such molecular responses. We used oligonucleotide arrays to study nearly 6000 genes in human SH-SY5Y neuroblastoma cells exposed to chronic ethanol. A set of 42 genes had consistently increased or decreased mRNA abundance after 3 days of ethanol treatment. Groups of genes related to norepinephrine production, glutathione metabolism and protection against apoptosis were identified. Genes involved in catecholamine metabolism are of special interest because of the role of this pathway in mediating ethanol withdrawal symptoms (physical dependence). Ethanol treatment elevated dopamine β-hydroxylase (DBH, EC 1.14.17.1) mRNA and protein levels and increased releasable norepinephrine in SH-SY5Y cultures. Acute ethanol also increased DBH mRNA levels in mouse adrenal gland, suggesting in vivo functional consequences for ethanol regulation of DBH. In SH-SY5Y cells, ethanol also decreased mRNA and secreted protein levels for monocyte chemotactic protein 1, an effect that could contribute to the protective role of moderate ethanol consumption in atherosclerotic vascular disease. Finally, we identified a subset of genes similarly regulated by both ethanol and dibutyryl-cAMP treatment in SH-SY5Y cells. This suggests that ethanol and cAMP signaling share mechanistic features in regulating a subset of ethanol-responsive genes. Our findings offer new insights regarding possible molecular mechanisms underlying behavioral responses or medical consequences of ethanol consumption and alcoholism.

Original languageEnglish (US)
Pages (from-to)1593-1600
Number of pages8
JournalMolecular Pharmacology
Volume58
Issue number6
StatePublished - 2000
Externally publishedYes

Fingerprint

Ethanol
Gene Expression
Genes
Messenger RNA
Oligonucleotide Array Sequence Analysis
Norepinephrine
Dopamine beta-Hydroxylase
Substance Withdrawal Syndrome
Chemokine CCL2
Adrenal Glands
Mixed Function Oxygenases
Neuroblastoma
Vascular Diseases
Alcoholism
Catecholamines
Glutathione
Dopamine
Proteins
Apoptosis

ASJC Scopus subject areas

  • Pharmacology

Cite this

Thibault, C., Lai, C., Wilke, N., Duong, B., Olive, M., Rahman, S., ... Miles, M. F. (2000). Expression profiling of neural cells reveals specific patterns of ethanol-responsive gene expression. Molecular Pharmacology, 58(6), 1593-1600.

Expression profiling of neural cells reveals specific patterns of ethanol-responsive gene expression. / Thibault, Christelle; Lai, Chaoqiang; Wilke, Norbert; Duong, Bao; Olive, Michael; Rahman, Sajida; Dong, Helin; Hodge, Clyde W.; Lockhart, David J.; Miles, Michael F.

In: Molecular Pharmacology, Vol. 58, No. 6, 2000, p. 1593-1600.

Research output: Contribution to journalArticle

Thibault, C, Lai, C, Wilke, N, Duong, B, Olive, M, Rahman, S, Dong, H, Hodge, CW, Lockhart, DJ & Miles, MF 2000, 'Expression profiling of neural cells reveals specific patterns of ethanol-responsive gene expression', Molecular Pharmacology, vol. 58, no. 6, pp. 1593-1600.
Thibault, Christelle ; Lai, Chaoqiang ; Wilke, Norbert ; Duong, Bao ; Olive, Michael ; Rahman, Sajida ; Dong, Helin ; Hodge, Clyde W. ; Lockhart, David J. ; Miles, Michael F. / Expression profiling of neural cells reveals specific patterns of ethanol-responsive gene expression. In: Molecular Pharmacology. 2000 ; Vol. 58, No. 6. pp. 1593-1600.
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