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Ischemia-induced STAT-1 expression and activation play a critical role in cardiomyocyte apoptosis

Stephanou, A; Brar, BK; Scarabelli, TM; Jonassen, AK; Yellon, DM; Marber, MS; Knight, RA; (2000) Ischemia-induced STAT-1 expression and activation play a critical role in cardiomyocyte apoptosis. J BIOL CHEM , 275 (14) 10002 - 10008. Gold open access

Abstract

We show here that exposure of cardiac cells to simulated ischemia results in apoptosis and is accompanied by phosphorylation and increased expression and transcriptional activity of STAT-1, Similarly, interferon-gamma, which is known to induce STAT-1 activation, also induced apoptosis in cardiac cells, STAT-1-transfected cells were more susceptible to ischemia-induced cell death than cells transfected with a control plasmid lacking the STAT-1 coding sequence. Furthermore, an antisense STAT-1 vector reduced both ischemia-and overexpressed STAT-1-induced cell death in cardiac cells. Both STAT-1 overexpression and interferon-gamma treatment or exposure to ischemia activated the promoter of the pro-apoptotic caspase-1 gene in cardiomyocytes. Finally, ischemia/reperfusion also induced STAT-1 activation and caspase-1 processing in ventricular myocytes in the intact heart er vivo. Immunofluorescent staining demonstrated an increase in STAT-1-positive staining in cardiomyocytes in response to ischemia/reperfusion that co-localized with terminal deoxynucleotidyl transferase dVTP nick end-labeling-positive apoptotic cells. These results suggest that STAT-1 plays a critical role in the regulation of ischemia/reperfusion-induced apoptosis in cardiac cells, acting at least in part via a caspase-1 activation-dependent pathway.

Type: Article
Title: Ischemia-induced STAT-1 expression and activation play a critical role in cardiomyocyte apoptosis
Open access status: An open access publication
Publisher version: http://www.jbc.org/content/early/recent/0
Keywords: SIGNAL-TRANSDUCTION, HEART-FAILURE, CELL-DEATH, PROTEIN, CARDIOTROPHIN-1, MYOCYTES, GP130, REPERFUSION, INFARCTION, CYTOKINE
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Institute of Cardiovascular Science
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Institute of Cardiovascular Science > Pre-clinical and Fundamental Science
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > UCL GOS Institute of Child Health > ICH - Directors Office
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > UCL GOS Institute of Child Health > ICH Genetics and Genomic Medicine Prog
URI: http://discovery.ucl.ac.uk/id/eprint/91139
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