STAT3 deletion sensitizes cells to oxidative stress.
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.
Barry
Seán P
SP
Medical Molecular Biology Unit, Institute of Child Health, University College London, 30 Guilford Street, London WC1N1EH, UK.
Townsend
Paul A
PA
McCormick
James
J
Knight
Richard A
RA
Scarabelli
Tiziano M
TM
Latchman
David S
DS
Stephanou
Anastasis
A
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
D050796:STAT3 Transcription Factor