[Todos] Seminarios conjuntos IFIBYNE-DFBMC- 26 de mayo -Leonardo Pignataro, Ph.D.

[Paula Felman]

Jueves 26 de mayo 13 Hs. en el aula de seminarios.

Leonardo Pignataro, Ph.D.

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]

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.

Leonardo Pignataro, Ph.D.
Assistant Professor of Clinical Aneshtesiology
Columbia University
College of Physicians & Surgeons
Dept. of Anesthesiology and Pharmacology
630 West 168th Street, P&S 7th Floor, Room 7-501
New York, NY 10032
Email <mailto:lp2391 en columbia.edu>lp2391 en columbia.edu
  Phone 212-305-4128 / 212-305-1929 Fax 212-305-3675
------------ próxima parte ------------
Se ha borrado un adjunto en formato HTML...
URL: http://mail.df.uba.ar/pipermail/todos/attachments/20110524/21c03792/attachment.html