The carboxyl-terminal activation domain of the STAT-1 transcription factor enhances ischemia/reperfusion-induced apoptosis in cardiac myocytes
Stephanou, Anastasis, Scarabelli, Tiziano M., Townsend, Paul A., Bell, Robert, Yellon, Derek, Knight, Richard A. and Latchman, David S. (2002) The carboxyl-terminal activation domain of the STAT-1 transcription factor enhances ischemia/reperfusion-induced apoptosis in cardiac myocytes. Federation of American Societies for Experimental Biology (FASEB) Journal, 16, (13), 1841-1843. (doi:10.1096/fj.02-0150fje).
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We have demonstrated previously that the STAT-1 transcription factor plays a key role in ischemia/reperfusion (I/R)-induced apoptosis in cardiac myocytes. In the present study we assessed which region of the STAT-1 molecule mediates apoptosis in cardiac myocytes. A STAT-1 construct (amino acid 350-750) lacking the N-terminus could enhance I/R-induced apoptosis in cardiac myocytes. However, a STAT-1 construct, which lacks 60 amino acids at the C-terminus (amino acid 691-750), was ineffective in promoting I/R-induced apoptosis in cardiac myocytes. Furthermore, overexpression of a C-terminal STAT-1 construct (amino acid 691-750) containing the transcriptional activation domain, but not the DNA binding domain, strongly enhanced I/R-induced apoptotic cell death. Cardiac myocytes isolated from mice expressing a truncated C-terminal STAT-1 were more sensitive to I/R-induced cell death. Finally, isolated hearts from these animals exposed to I/R injury had larger infarct size and greater number of TUNEL-positive myocytes than control hearts. These studies demonstrate that the C-terminal transactivation domain of STAT-1 is necessary and sufficient for I/R injury-induced apoptosis in cardiac myocytes.
|Keywords:||apoptosis, dna, serine, injuries, myocardial infarction, dna-binding proteins, mice, child, myocardial reperfusion injury, genetics, physiopathology, pathology,acid, physiology, phosphorylation|
Q Science > QR Microbiology
|Divisions:||University Structure - Pre August 2011 > School of Medicine > Infection, Inflammation and Repair
University Structure - Pre August 2011 > School of Medicine
University Structure - Pre August 2011 > School of Medicine > Human Genetics
|Date Deposited:||08 Sep 2008|
|Last Modified:||02 Mar 2012 11:31|
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