Premium
The C‐terminal activation domain of the STAT‐1 transcription enhances ischemia/reperfusion‐induced apoptosis in cardiac myocytes
Author(s) -
Stephanou Anastasis,
Scarabelli Tiziano M.,
Townsend Paul A.,
Bell Robert,
Yellon Derek,
Knight Richard A.,
Latchman David S.
Publication year - 2002
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.02-0150fje
Subject(s) - myocyte , apoptosis , transactivation , tunel assay , transcription factor , stat , microbiology and biotechnology , programmed cell death , biology , chemistry , biochemistry , stat3 , gene
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.