Induction of apoptosis and Fas receptor/Fas ligand expression by ischemia/reperfusion in cardiac myocytes requires serine 727 of the STAT-1 transcription factor but not tyrosine 701. The Journal of biological chemistry. [J Biol Chem] Journal article

Title	Induction of apoptosis and Fas receptor/Fas ligand expression by ischemia/reperfusion in cardiac myocytes requires serine 727 of the STAT-1 transcription factor but not tyrosine 701.
Author(s)	Stephanou A, Scarabelli TM, Brar BK, Nakanishi Y, Matsumura M, Knight RA, Latchman DS
Institution	Medical Molecular Biology Unit, Institute of Child Health, University College London, 30 Guilford Street, London, WC1N 1EH, United Kingdom. A.Stephanou@ich.ucl.ac.uk
Source	J Biol Chem 2001 Jul 27; 276(30):28340-7.
MeSH	Animals Animals, Newborn Antigens, CD95 Apoptosis Blotting, Western Cells, Cultured DNA DNA-Binding Proteins Enzyme Inhibitors Imidazoles In Situ Nick-End Labeling Membrane Glycoproteins Microscopy, Fluorescence Mitogen-Activated Protein Kinase 1 Mitogen-Activated Protein Kinases Myocardium Phosphorylation Plasmids Pyridines Rats Rats, Sprague-Dawley Reperfusion Injury STAT1 Transcription Factor Serine Signal Transduction Trans-Activation (Genetics) Trans-Activators Transfection Tyrosine p38 Mitogen-Activated Protein Kinases
Abstract	Previously we reported that ischemia results in apoptosis and is accompanied by phosphorylation on Tyr-701 and increased expression and transcriptional activity of the signal transducer and activator of transcription-1 (STAT-1). In the present study, we show that exposure of cardiomyocytes to ischemia induced the phosphorylation of STAT-1 at another site, Ser-727. Moreover, STAT-1 is critical for the induction of Fas receptor and Fas ligand expression by ischemia/reperfusion (I/R). Transcriptional activation of Fas and FasL was dependent on Ser-727 of STAT-1 but was independent of Tyr-701. Similarly, Ser-727 but not Tyr-701 was required for enhancement of cardiomyocyte cell death by STAT-1 during I/R. In addition, inhibition of the p38 pathway prevented the induction and transcriptional activation of Fas and FasL in cardiac cells exposed to I/R, whereas inhibition of p42/p44 MAPK had no effect. Finally, I/R also induced phosphorylation of STAT-1 on Ser-727 and expression of Fas/FasL in ventricular myocytes in the intact heart ex vivo. These results indicate that Fas/FasL genes and apoptosis are activated by STAT-1 in cardiac myocytes exposed to I/R and these effects are dependent on the Ser-727 but not the Tyr-701 phosphorylation sites of STAT-1.
Language	eng
Pub Type(s)	Journal Article
PubMed ID	11309387

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