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Jueves 26 de mayo<b> </b>13 Hs. en el aula de seminarios.<br>
<b> <br>
</b>Leonardo Pignataro, Ph.D.<br>
<b> <br>
</b>Titulo: "Alcohol and heat shock regulate gene expression in the
brain" [El alcohol y el stress termico regulan la expression de
genes en la corteza] <br>
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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. In order
to elucidate these mechanisms, we investigated Gabra4, a neuron-specific
gene that is rapidly and robustly activated by alcohol (10 – 60 mM), 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. Micro-array
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.<br>
<br>
Leonardo Pignataro, Ph.D. <br>
Assistant Professor of Clinical Aneshtesiology <br>
Columbia University<br>
College of Physicians & Surgeons <br>
Dept. of Anesthesiology and Pharmacology <br>
630 West 168th Street, P&S 7th Floor, Room 7-501<br>
New York, NY 10032 <br>
Email <a href="mailto:lp2391@columbia.edu">lp2391@columbia.edu</a><br>
Phone 212-305-4128 / 212-305-1929 Fax 212-305-3675<br>
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