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The carboxyl-terminal activation domain of the STAT-1 transcription factor enhances ischemia/reperfusion-induced apoptosis in cardiac myocytes

Record type: Article

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.

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Citation

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 The FASEB Journal, 16, (13), pp. 1841-1843. (doi:10.1096/fj.02-0150fje).

More information

Published date: 5 September 2002
Keywords: apoptosis, dna, serine, injuries, myocardial infarction, dna-binding proteins, mice, child, myocardial reperfusion injury, genetics, physiopathology, pathology, acid, physiology, phosphorylation
Organisations: Human Genetics, Infection Inflammation & Immunity, Medicine

Identifiers

Local EPrints ID: 60262
URI: http://eprints.soton.ac.uk/id/eprint/60262
ISSN: 0892-6638
PURE UUID: 6dd92fa2-ac70-4736-9896-20de19406585

Catalogue record

Date deposited: 08 Sep 2008
Last modified: 17 Jul 2017 14:23

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Contributors

Author: Anastasis Stephanou
Author: Tiziano M. Scarabelli
Author: Paul A. Townsend
Author: Robert Bell
Author: Derek Yellon
Author: Richard A. Knight
Author: David S. Latchman

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