Journal article
Alcohol Regulates Gene Expression in Neurons via Activation of Heat Shock Factor 1
The Journal of neuroscience, Vol.27(47), pp.12957-12966
11/21/2007
DOI: 10.1523/JNEUROSCI.4142-07.2007
PMCID: PMC6673276
PMID: 18032669
Abstract
Drinking alcohol causes widespread alterations in gene expression that can result in long-term physiological changes. Although many alcohol-responsive genes (ARGs) have been identified, the mechanisms by which alcohol alters transcription are not well understood. To elucidate these mechanisms, we investigated
Gabra4
, a neuron-specific gene that is rapidly and robustly activated by alcohol (10–60 m
m
), both
in vitro
and
in vivo
. Here we show that alcohol can activate elements of the heat shock pathway in mouse cortical neurons to enhance the expression of
Gabra4
and other ARGs. The activation of
Gabra4
by alcohol or high temperature is dependent on the binding of heat shock factor 1 (HSF1) to a short downstream DNA sequence, the alcohol response element (ARE). Alcohol and heat stimulate the translocation of HSF1 from the cytoplasm to the nucleus and the induction of HSF1-dependent genes,
Hsp70
and
Hsp90
, in cultured neurons and in the mouse cerebral cortex
in vivo
. The reduction of HSF1 levels using small interfering RNA prevented the stimulation of
Gabra4
and
Hsp70
by alcohol and heat shock. Microarray analysis showed that many ARGs contain ARE-like sequences and that some of these genes are also activated by heat shock. We suggest that alcohol activates phylogenetically conserved pathways that involve intermediates in the heat shock cascade and that sequence elements similar to the ARE may mediate some of the changes in gene expression triggered by alcohol intake, which could be important in a variety of pathophysiological responses to alcohol.
Details
- Title: Subtitle
- Alcohol Regulates Gene Expression in Neurons via Activation of Heat Shock Factor 1
- Creators
- Leonardo Pignataro - Departments of Anesthesiology, Pharmacology, andAlexandria N. Miller - Departments of Anesthesiology, Pharmacology, andLimei Ma - Stowers Institute for Medical ResearchShonali Midha - Psychiatry, Weill Cornell Medical College, New York, New York 10021Petr Protiva - University of Connecticut Health CenterDaniel G. Herrera - Psychiatry, Weill Cornell Medical College, New York, New York 10021Neil L. Harrison - Departments of Anesthesiology, Pharmacology, and
- Resource Type
- Journal article
- Publication Details
- The Journal of neuroscience, Vol.27(47), pp.12957-12966
- Publisher
- Society for Neuroscience
- DOI
- 10.1523/JNEUROSCI.4142-07.2007
- PMID
- 18032669
- PMCID
- PMC6673276
- ISSN
- 0270-6474
- eISSN
- 1529-2401
- Language
- English
- Date published
- 11/21/2007
- Academic Unit
- Molecular Physiology and Biophysics
- Record Identifier
- 9984446070002771
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