title: STAT3 deletion sensitizes cells to oxidative stress.
abstract: The transcription factor STAT1 plays a role in promoting apoptotic cell death, whereas the related STAT3 transcription factor protects cardiac myocytes from ischemia/reperfusion (I/R) injury or oxidative stress. Cytokines belonging to the IL-6 family activate the JAK-STAT3 pathway, but also activate other cytoprotective pathways such as the MAPK-ERK or the PI3-AKT pathway. It is therefore unclear whether STAT3 is the only cytoprotective mediator against oxidative stress-induced cell death. Overexpression of STAT3 in primary neonatal rat ventricular myocytes (NRVM) protects against I/R-induced cell death. Moreover, a dominant negative STAT3 adenovirus (Ad ST3-DN) enhanced apoptotic cell death (81.2+/-6.9%) compared to control infected NRVM (46.0+/-3.1%) following I/R. Depletion of STAT3 sensitized cells to apoptotic cell death following oxidative stress. These results provide direct evidence for the role of STAT3 as a cytoprotective transcription factor in cells exposed to oxidative stress.
authors.affiliation: Medical Molecular Biology Unit, Institute of Child Health, University College London, 30 Guilford Street, London WC1N1EH, UK.
authors.forename: Seán P
authors.initials: SP
authors.lastname: Barry
authors.forename: Paul A
authors.initials: PA
authors.lastname: Townsend
authors.forename: James
authors.initials: J
authors.lastname: McCormick
authors.forename: Richard A
authors.initials: RA
authors.lastname: Knight
authors.forename: Tiziano M
authors.initials: TM
authors.lastname: Scarabelli
authors.forename: David S
authors.initials: DS
authors.lastname: Latchman
authors.forename: Anastasis
authors.initials: A
authors.lastname: Stephanou
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002460:Cell Line; D017353:Gene Deletion; D051379:Mice; D009154:Mutation; D015428:Myocardial Reperfusion Injury / Q000235:genetics*; D032383:Myocytes, Cardiac / Q000378:metabolism*; D018384:Oxidative Stress / Q000235:genetics*; D051381:Rats; D050796:STAT3 Transcription Factor / Q000172:deficiency* / Q000235:genetics
chemical_list: D050796:STAT3 Transcription Factor